Lung Cancer

Oral apixaban (Eliquis, Bristol-Myers Squibb/Pfizer) was as effective as subcutaneous dalteparin (Fragmin, Pfizer) for cancer-related venous thromboembolism (VTE) without an increased risk of major bleeding, the CARAVAGGIO study suggests.

Over 6 months of follow-up, the primary efficacy outcome of recurrent thromboembolism occurred in 32 of 576 patients (5.6%) randomly assigned to apixaban and in 46 of 579 patients (7.9%) assigned dalteparin (hazard ratio, 0.63; 95% confidence interval, 0.37-1.07). The risk difference met the criteria for noninferiority (P < .001) but not for superiority (P = .09).

The risk for major bleeding was similar in the apixaban and dalteparin groups (3.8% and 4.0%; P = .60), including major gastrointestinal (GI) bleeds (11 vs 10 events). 

There was a numeric excess of clinically relevant nonmajor bleeding in the apixaban group (9.0% vs 6.0%; HR, 1.42; 95% CI, 0.88-2.30).

However, the site of this bleeding “was essentially the genitourinary tract and the upper respiratory tract, so again there was no increase in gastrointestinal bleeding, even when the clinically relevant major bleeding was considered,” said lead author Giancarlo Agnelli, MD, University of Perugia, Italy.

Taken together, “We believe that the findings of CARAVAGGIO expand the proportion of patients with cancer-associated thrombosis who are eligible for treatment with oral direct anticoagulants, including patients with gastrointestinal cancer,” he concluded.

The findings were presented online March 29 at the American College of Cardiology 2020 Scientific Session (ACC.20)/World Congress of Cardiology (WCC) and published simultaneously in the New England Journal of Medicine.

Major guidelines recommend the use of low-molecular-weight heparin (LMWH) for the treatment of cancer-related VTE but also support the use of edoxaban (Savaysa, Daiichi Sankyo) and rivaroxaban (Xarelto, Janssen Pharmaceuticals) as an alternative based on data from the OKUSAI VTE and SELECT-D trials, respectively. But an increased risk for bleeding was observed among patients with GI cancer in both studies.

“The findings are of clinical relevance because we were able to confirm the efficacy of another [novel oral anticoagulant] NOAC but we have the absence of bleeding, GI bleeding in particular. This is an important point; this is what the clinical community is looking for,” Agnelli told theheart.org | Medscape Cardiology.

The recent ADAM VTE trial testing apixaban, a factor Xa inhibitor, vs dalteparin, a LMWH, reported no major bleeding among patients treated with apixaban (primary safety endpoint) and a significant reduction of VTE (secondary efficacy endpoint). But the trial included only 300 patients with cancer and a more selected population compared with the CARAVAGGIO trial, noted Chiara Melloni, MD, MHS, a cardiologist at Duke Clinical Research Institute, Durham, North Carolina, who was not involved with the trial.

“The trial presented today by Prof. Agnelli provides evidence that apixaban represents an additional valid option, next to edoxaban and rivaroxaban, for the treatment of VTE in cancer patients,” she told theheart.org | Medscape Cardiology in an email. “The subgroup analyses showed consistent results across all different subgroups, but a significant interaction was observed between age groups, with a more favorable profile among those less than 75 years old (and mostly among those <65 years old). This may require more investigation.”

The CARAVAGGIO investigators randomly assigned 576 consecutive patients with cancer who had newly diagnosed symptomatic or incidental acute proximal deep-vein thrombosis or pulmonary embolism to receive apixaban 10 mg twice daily for 7 days followed by 5 mg twice daily or subcutaneous dalteparin 200 IU per kg once daily for 1 month followed by 150 U/kg once daily, both for a total of 6 months. Dose reduction was allowed for dalteparin but not for apixaban during the study.

Various types of cancer were included in the trial, including lung, breast, genitourinary, and upper GI.

The incidence of death was similar in the apixaban and dalteparin groups (23.4% vs 26.4%), with most deaths related to cancer (85.2% vs 88.2%, respectively).

During a discussion of the findings, panelist Bonnie Ky, MD, from the Hospital of the University of Pennsylvania in Philadelphia, and editor in chief of JACC: CardioOncology, congratulated the authors on an “excellent, well-done study” in a high-need cancer population suffering from a clinically significant burden of VTE, reported to be anywhere from 8% to 19% depending on tumor type.

“I was particularly impressed by the low rate of bleeding, which has been traditionally a concern with DOACs, as well the demonstration of noninferiority of apixaban,” she said.

Ky asked why the bleeding rate was lower than observed in other published studies and in whom clinicians shouldn’t be considering apixaban now.

Agnelli said that a head-to-head study is needed to compare the various oral anticoagulant agents but that the gastrointestinal bleeding rate is well known to be reduced with apixaban in patients with atrial fibrillation.

“So whether this is related to the drug or the administration twice daily, it’s something that can be discussed, but honestly the final solution would be to have a comparative study,” he said. “It’s going to be difficult, but it’s what we need.”

As to the clinical application of the data, Agnelli said, “The apixaban data actually extend the number of our patients who could receive the oral agents, including patients with GI cancer. So I do believe this indication about using DOACs in cancer patients will change and the indication expanded. But of course, we are building on something that was already known. We did not discover this all by ourselves.”

Panelist Robert M. Carey, MD, a leader in cardiovascular endocrinology and dean emeritus, University of Virginia School of Medicine  in Charlottesville, said the study “conclusively shows noninferiority” but asked for more detail on the subset of patients with GI malignancies and the bleeding rate there.

Agnelli replied that the proportion and number of these patients in CARAVAGGIO is the same as, if not slightly higher than, in other studies. “So we have a population that is representative of all the cancer population, including GI cancer,” he said, adding that subanalyses are underway correlating the site of cancer with the type of bleeding.

Agnes Y.Y. Lee, MD, University of British Columbia, Vancouver Coastal Health, and the British Cancer Agency, all in Vancouver, Canada, notes in a linked editorial that CARAVAGGIO excluded patients with primary and metastatic brain lesions and included few patients with cancers of the upper GI tract, with hematologic cancers, or receiving newer cancer therapies, such as checkpoint inhibitors.

She says clinicians will have to choose carefully which anticoagulant to use but that LMWH is “preferred in patients in whom drug-drug interaction is a concern and in those who have undergone surgery involving the upper gastrointestinal tract because absorption of all direct oral anticoagulants occurs in the stomach or proximal small bowel.”

Warfarin may also be the only option when cost is the “decision driver” in patients with cancer facing major financial healthcare burdens, Lee writes.

Duke’s Melloni also said the cost of oral anticoagulants needs to be taken into account and varies widely for patients based on their insurance and availability of other copay assistance programs. “It is therefore important to discuss with the patients upfront because if the patients are started but cannot afford long term, early discontinuation can impact their safety,” she said.

The trial was sponsored by FADOI (Federazione delle Associazioni dei Dirigenti Ospedalieri Internisti) and was funded by an unrestricted grant from the Bristol-Myers Squibb-Pfizer Alliance. Agnelli reports personal fees from Pfizer and Bayer Healthcare, and “other” from Daiichi Sankyo outside the submitted work. Melloni reports having no relevant conflicts of interest. Lee reports personal fees and nonfinancial support from Bayer; grants, personal fees, and nonfinancial support from Bristol-Myers Squibb; and personal fees from LEO Pharma, Pfizer, and Quercegen Pharmaceuticals outside the submitted work.

This article first appeared on Medscape.com.

Oral apixaban (Eliquis, Bristol-Myers Squibb/Pfizer) was as effective as subcutaneous dalteparin (Fragmin, Pfizer) for cancer-related venous thromboembolism (VTE) without an increased risk of major bleeding, the CARAVAGGIO study suggests.

Over 6 months of follow-up, the primary efficacy outcome of recurrent thromboembolism occurred in 32 of 576 patients (5.6%) randomly assigned to apixaban and in 46 of 579 patients (7.9%) assigned dalteparin (hazard ratio, 0.63; 95% confidence interval, 0.37-1.07). The risk difference met the criteria for noninferiority (P < .001) but not for superiority (P = .09).

The risk for major bleeding was similar in the apixaban and dalteparin groups (3.8% and 4.0%; P = .60), including major gastrointestinal (GI) bleeds (11 vs 10 events). 

There was a numeric excess of clinically relevant nonmajor bleeding in the apixaban group (9.0% vs 6.0%; HR, 1.42; 95% CI, 0.88-2.30).

However, the site of this bleeding “was essentially the genitourinary tract and the upper respiratory tract, so again there was no increase in gastrointestinal bleeding, even when the clinically relevant major bleeding was considered,” said lead author Giancarlo Agnelli, MD, University of Perugia, Italy.

Taken together, “We believe that the findings of CARAVAGGIO expand the proportion of patients with cancer-associated thrombosis who are eligible for treatment with oral direct anticoagulants, including patients with gastrointestinal cancer,” he concluded.

The findings were presented online March 29 at the American College of Cardiology 2020 Scientific Session (ACC.20)/World Congress of Cardiology (WCC) and published simultaneously in the New England Journal of Medicine.

Major guidelines recommend the use of low-molecular-weight heparin (LMWH) for the treatment of cancer-related VTE but also support the use of edoxaban (Savaysa, Daiichi Sankyo) and rivaroxaban (Xarelto, Janssen Pharmaceuticals) as an alternative based on data from the OKUSAI VTE and SELECT-D trials, respectively. But an increased risk for bleeding was observed among patients with GI cancer in both studies.

“The findings are of clinical relevance because we were able to confirm the efficacy of another [novel oral anticoagulant] NOAC but we have the absence of bleeding, GI bleeding in particular. This is an important point; this is what the clinical community is looking for,” Agnelli told theheart.org | Medscape Cardiology.

The recent ADAM VTE trial testing apixaban, a factor Xa inhibitor, vs dalteparin, a LMWH, reported no major bleeding among patients treated with apixaban (primary safety endpoint) and a significant reduction of VTE (secondary efficacy endpoint). But the trial included only 300 patients with cancer and a more selected population compared with the CARAVAGGIO trial, noted Chiara Melloni, MD, MHS, a cardiologist at Duke Clinical Research Institute, Durham, North Carolina, who was not involved with the trial.

“The trial presented today by Prof. Agnelli provides evidence that apixaban represents an additional valid option, next to edoxaban and rivaroxaban, for the treatment of VTE in cancer patients,” she told theheart.org | Medscape Cardiology in an email. “The subgroup analyses showed consistent results across all different subgroups, but a significant interaction was observed between age groups, with a more favorable profile among those less than 75 years old (and mostly among those <65 years old). This may require more investigation.”

The CARAVAGGIO investigators randomly assigned 576 consecutive patients with cancer who had newly diagnosed symptomatic or incidental acute proximal deep-vein thrombosis or pulmonary embolism to receive apixaban 10 mg twice daily for 7 days followed by 5 mg twice daily or subcutaneous dalteparin 200 IU per kg once daily for 1 month followed by 150 U/kg once daily, both for a total of 6 months. Dose reduction was allowed for dalteparin but not for apixaban during the study.

Various types of cancer were included in the trial, including lung, breast, genitourinary, and upper GI.

The incidence of death was similar in the apixaban and dalteparin groups (23.4% vs 26.4%), with most deaths related to cancer (85.2% vs 88.2%, respectively).

During a discussion of the findings, panelist Bonnie Ky, MD, from the Hospital of the University of Pennsylvania in Philadelphia, and editor in chief of JACC: CardioOncology, congratulated the authors on an “excellent, well-done study” in a high-need cancer population suffering from a clinically significant burden of VTE, reported to be anywhere from 8% to 19% depending on tumor type.

“I was particularly impressed by the low rate of bleeding, which has been traditionally a concern with DOACs, as well the demonstration of noninferiority of apixaban,” she said.

Ky asked why the bleeding rate was lower than observed in other published studies and in whom clinicians shouldn’t be considering apixaban now.

Agnelli said that a head-to-head study is needed to compare the various oral anticoagulant agents but that the gastrointestinal bleeding rate is well known to be reduced with apixaban in patients with atrial fibrillation.

“So whether this is related to the drug or the administration twice daily, it’s something that can be discussed, but honestly the final solution would be to have a comparative study,” he said. “It’s going to be difficult, but it’s what we need.”

As to the clinical application of the data, Agnelli said, “The apixaban data actually extend the number of our patients who could receive the oral agents, including patients with GI cancer. So I do believe this indication about using DOACs in cancer patients will change and the indication expanded. But of course, we are building on something that was already known. We did not discover this all by ourselves.”

Panelist Robert M. Carey, MD, a leader in cardiovascular endocrinology and dean emeritus, University of Virginia School of Medicine  in Charlottesville, said the study “conclusively shows noninferiority” but asked for more detail on the subset of patients with GI malignancies and the bleeding rate there.

Agnelli replied that the proportion and number of these patients in CARAVAGGIO is the same as, if not slightly higher than, in other studies. “So we have a population that is representative of all the cancer population, including GI cancer,” he said, adding that subanalyses are underway correlating the site of cancer with the type of bleeding.

Agnes Y.Y. Lee, MD, University of British Columbia, Vancouver Coastal Health, and the British Cancer Agency, all in Vancouver, Canada, notes in a linked editorial that CARAVAGGIO excluded patients with primary and metastatic brain lesions and included few patients with cancers of the upper GI tract, with hematologic cancers, or receiving newer cancer therapies, such as checkpoint inhibitors.

She says clinicians will have to choose carefully which anticoagulant to use but that LMWH is “preferred in patients in whom drug-drug interaction is a concern and in those who have undergone surgery involving the upper gastrointestinal tract because absorption of all direct oral anticoagulants occurs in the stomach or proximal small bowel.”

Warfarin may also be the only option when cost is the “decision driver” in patients with cancer facing major financial healthcare burdens, Lee writes.

Duke’s Melloni also said the cost of oral anticoagulants needs to be taken into account and varies widely for patients based on their insurance and availability of other copay assistance programs. “It is therefore important to discuss with the patients upfront because if the patients are started but cannot afford long term, early discontinuation can impact their safety,” she said.

The trial was sponsored by FADOI (Federazione delle Associazioni dei Dirigenti Ospedalieri Internisti) and was funded by an unrestricted grant from the Bristol-Myers Squibb-Pfizer Alliance. Agnelli reports personal fees from Pfizer and Bayer Healthcare, and “other” from Daiichi Sankyo outside the submitted work. Melloni reports having no relevant conflicts of interest. Lee reports personal fees and nonfinancial support from Bayer; grants, personal fees, and nonfinancial support from Bristol-Myers Squibb; and personal fees from LEO Pharma, Pfizer, and Quercegen Pharmaceuticals outside the submitted work.

This article first appeared on Medscape.com.

Oral apixaban (Eliquis, Bristol-Myers Squibb/Pfizer) was as effective as subcutaneous dalteparin (Fragmin, Pfizer) for cancer-related venous thromboembolism (VTE) without an increased risk of major bleeding, the CARAVAGGIO study suggests.

Over 6 months of follow-up, the primary efficacy outcome of recurrent thromboembolism occurred in 32 of 576 patients (5.6%) randomly assigned to apixaban and in 46 of 579 patients (7.9%) assigned dalteparin (hazard ratio, 0.63; 95% confidence interval, 0.37-1.07). The risk difference met the criteria for noninferiority (P < .001) but not for superiority (P = .09).

The risk for major bleeding was similar in the apixaban and dalteparin groups (3.8% and 4.0%; P = .60), including major gastrointestinal (GI) bleeds (11 vs 10 events). 

There was a numeric excess of clinically relevant nonmajor bleeding in the apixaban group (9.0% vs 6.0%; HR, 1.42; 95% CI, 0.88-2.30).

However, the site of this bleeding “was essentially the genitourinary tract and the upper respiratory tract, so again there was no increase in gastrointestinal bleeding, even when the clinically relevant major bleeding was considered,” said lead author Giancarlo Agnelli, MD, University of Perugia, Italy.

Taken together, “We believe that the findings of CARAVAGGIO expand the proportion of patients with cancer-associated thrombosis who are eligible for treatment with oral direct anticoagulants, including patients with gastrointestinal cancer,” he concluded.

The findings were presented online March 29 at the American College of Cardiology 2020 Scientific Session (ACC.20)/World Congress of Cardiology (WCC) and published simultaneously in the New England Journal of Medicine.

Major guidelines recommend the use of low-molecular-weight heparin (LMWH) for the treatment of cancer-related VTE but also support the use of edoxaban (Savaysa, Daiichi Sankyo) and rivaroxaban (Xarelto, Janssen Pharmaceuticals) as an alternative based on data from the OKUSAI VTE and SELECT-D trials, respectively. But an increased risk for bleeding was observed among patients with GI cancer in both studies.

“The findings are of clinical relevance because we were able to confirm the efficacy of another [novel oral anticoagulant] NOAC but we have the absence of bleeding, GI bleeding in particular. This is an important point; this is what the clinical community is looking for,” Agnelli told theheart.org | Medscape Cardiology.

The recent ADAM VTE trial testing apixaban, a factor Xa inhibitor, vs dalteparin, a LMWH, reported no major bleeding among patients treated with apixaban (primary safety endpoint) and a significant reduction of VTE (secondary efficacy endpoint). But the trial included only 300 patients with cancer and a more selected population compared with the CARAVAGGIO trial, noted Chiara Melloni, MD, MHS, a cardiologist at Duke Clinical Research Institute, Durham, North Carolina, who was not involved with the trial.

“The trial presented today by Prof. Agnelli provides evidence that apixaban represents an additional valid option, next to edoxaban and rivaroxaban, for the treatment of VTE in cancer patients,” she told theheart.org | Medscape Cardiology in an email. “The subgroup analyses showed consistent results across all different subgroups, but a significant interaction was observed between age groups, with a more favorable profile among those less than 75 years old (and mostly among those <65 years old). This may require more investigation.”

The CARAVAGGIO investigators randomly assigned 576 consecutive patients with cancer who had newly diagnosed symptomatic or incidental acute proximal deep-vein thrombosis or pulmonary embolism to receive apixaban 10 mg twice daily for 7 days followed by 5 mg twice daily or subcutaneous dalteparin 200 IU per kg once daily for 1 month followed by 150 U/kg once daily, both for a total of 6 months. Dose reduction was allowed for dalteparin but not for apixaban during the study.

Various types of cancer were included in the trial, including lung, breast, genitourinary, and upper GI.

The incidence of death was similar in the apixaban and dalteparin groups (23.4% vs 26.4%), with most deaths related to cancer (85.2% vs 88.2%, respectively).

During a discussion of the findings, panelist Bonnie Ky, MD, from the Hospital of the University of Pennsylvania in Philadelphia, and editor in chief of JACC: CardioOncology, congratulated the authors on an “excellent, well-done study” in a high-need cancer population suffering from a clinically significant burden of VTE, reported to be anywhere from 8% to 19% depending on tumor type.

“I was particularly impressed by the low rate of bleeding, which has been traditionally a concern with DOACs, as well the demonstration of noninferiority of apixaban,” she said.

Ky asked why the bleeding rate was lower than observed in other published studies and in whom clinicians shouldn’t be considering apixaban now.

Agnelli said that a head-to-head study is needed to compare the various oral anticoagulant agents but that the gastrointestinal bleeding rate is well known to be reduced with apixaban in patients with atrial fibrillation.

“So whether this is related to the drug or the administration twice daily, it’s something that can be discussed, but honestly the final solution would be to have a comparative study,” he said. “It’s going to be difficult, but it’s what we need.”

As to the clinical application of the data, Agnelli said, “The apixaban data actually extend the number of our patients who could receive the oral agents, including patients with GI cancer. So I do believe this indication about using DOACs in cancer patients will change and the indication expanded. But of course, we are building on something that was already known. We did not discover this all by ourselves.”

Panelist Robert M. Carey, MD, a leader in cardiovascular endocrinology and dean emeritus, University of Virginia School of Medicine  in Charlottesville, said the study “conclusively shows noninferiority” but asked for more detail on the subset of patients with GI malignancies and the bleeding rate there.

Agnelli replied that the proportion and number of these patients in CARAVAGGIO is the same as, if not slightly higher than, in other studies. “So we have a population that is representative of all the cancer population, including GI cancer,” he said, adding that subanalyses are underway correlating the site of cancer with the type of bleeding.

Agnes Y.Y. Lee, MD, University of British Columbia, Vancouver Coastal Health, and the British Cancer Agency, all in Vancouver, Canada, notes in a linked editorial that CARAVAGGIO excluded patients with primary and metastatic brain lesions and included few patients with cancers of the upper GI tract, with hematologic cancers, or receiving newer cancer therapies, such as checkpoint inhibitors.

She says clinicians will have to choose carefully which anticoagulant to use but that LMWH is “preferred in patients in whom drug-drug interaction is a concern and in those who have undergone surgery involving the upper gastrointestinal tract because absorption of all direct oral anticoagulants occurs in the stomach or proximal small bowel.”

Warfarin may also be the only option when cost is the “decision driver” in patients with cancer facing major financial healthcare burdens, Lee writes.

Duke’s Melloni also said the cost of oral anticoagulants needs to be taken into account and varies widely for patients based on their insurance and availability of other copay assistance programs. “It is therefore important to discuss with the patients upfront because if the patients are started but cannot afford long term, early discontinuation can impact their safety,” she said.

The trial was sponsored by FADOI (Federazione delle Associazioni dei Dirigenti Ospedalieri Internisti) and was funded by an unrestricted grant from the Bristol-Myers Squibb-Pfizer Alliance. Agnelli reports personal fees from Pfizer and Bayer Healthcare, and “other” from Daiichi Sankyo outside the submitted work. Melloni reports having no relevant conflicts of interest. Lee reports personal fees and nonfinancial support from Bayer; grants, personal fees, and nonfinancial support from Bristol-Myers Squibb; and personal fees from LEO Pharma, Pfizer, and Quercegen Pharmaceuticals outside the submitted work.

This article first appeared on Medscape.com.

The US Food and Drug Administration has approved the immunotherapy durvalumab (Imfinzi, AstraZeneca) in combination with etoposide and either carboplatin or cisplatin as first-line treatment of patients with extensive-stage small cell lung cancer (ES-SCLC).

Durvalumab plus chemotherapy “can be considered a new standard in ES-SCLC,” said Myung-Ju Ahn, MD, Sungkyunkwan University, Seoul, South Korea, last year at the European Society of Medical Oncology (ESMO) annual meeting, where he discussed results from the phase 3 trial known as CASPIAN.

The new approval is based on efficacy and safety data from that trial, conducted in patients with previously untreated ES-SCLC. In the experimental group (n = 268), durvalumab plus etoposide and a platinum agent (EP) was followed by maintenance durvalumab, and in the control group (n = 269) patients received the EP regimen alone.

Median overall survival (OS) was 13 months in the durvalumab plus chemotherapy group compared with 10.3 months in the chemotherapy alone group (hazard ratio 0.73; 95% confidence interval, 0.59-0.91; P = .0047).

Reporting these results, trial investigator Luis Paz-Ares, MD, Hospital Universitario 12 de Octubre, Madrid, put the new survival benefit in the context of standard treatments at the ESMO meeting last year.

“Initial response rates to etoposide plus a platinum are high, but responses are not durable and patients treated with EP typically relapse within 6 months of starting treatment with a median OS of approximately 10 months,” he said.

In addition to the primary endpoint of OS, additional efficacy outcome measures were investigator-assessed progression-free survival (PFS) and objective response rate (ORR).

Median PFS was not statistically significant with immunotherapy; it was 5.1 months (95% CI, 4.7-6.2) in the durvalumab plus chemotherapy group and 5.4 months (95% CI, 4.8-6.2) in the chemotherapy alone group (HR, 0.78; 95% CI, 0.65-0.94).

The investigator-assessed ORR was 68% in the durvalumab plus chemotherapy group and 58% in the chemotherapy alone group.

The most common adverse reactions (≥ 20%) in patients with ES-SCLC were nausea, fatigue/asthenia, and alopecia, according to the FDA.

At ESMO, Paz-Ares reported that rates of serious adverse events (AEs) were comparable at 30.9% and 36.1% for the durvalumab plus EP group vs. EP alone, respectively; rates of AEs leading to discontinuation were identical in both groups at 9.4%. Unsurprisingly, immune-mediated AEs were higher at 19.6% in the durvalumab combination group vs. 2.6% in the EP alone group.

In this setting, durvalumab is administered prior to chemotherapy on the same day. The recommended durvalumab dose (when administered with etoposide and carboplatin or cisplatin) is 1,500 mg every 3 weeks prior to chemotherapy and then every 4 weeks as a single-agent maintenance therapy.

Durvalumab is already approved for metastatic non–small cell lung cancer in patients whose tumors have only spread in the chest, and is also approved for use in urothelial cancer.

This article first appeared on Medscape.com.

The US Food and Drug Administration has approved the immunotherapy durvalumab (Imfinzi, AstraZeneca) in combination with etoposide and either carboplatin or cisplatin as first-line treatment of patients with extensive-stage small cell lung cancer (ES-SCLC).

Durvalumab plus chemotherapy “can be considered a new standard in ES-SCLC,” said Myung-Ju Ahn, MD, Sungkyunkwan University, Seoul, South Korea, last year at the European Society of Medical Oncology (ESMO) annual meeting, where he discussed results from the phase 3 trial known as CASPIAN.

The new approval is based on efficacy and safety data from that trial, conducted in patients with previously untreated ES-SCLC. In the experimental group (n = 268), durvalumab plus etoposide and a platinum agent (EP) was followed by maintenance durvalumab, and in the control group (n = 269) patients received the EP regimen alone.

Median overall survival (OS) was 13 months in the durvalumab plus chemotherapy group compared with 10.3 months in the chemotherapy alone group (hazard ratio 0.73; 95% confidence interval, 0.59-0.91; P = .0047).

Reporting these results, trial investigator Luis Paz-Ares, MD, Hospital Universitario 12 de Octubre, Madrid, put the new survival benefit in the context of standard treatments at the ESMO meeting last year.

“Initial response rates to etoposide plus a platinum are high, but responses are not durable and patients treated with EP typically relapse within 6 months of starting treatment with a median OS of approximately 10 months,” he said.

In addition to the primary endpoint of OS, additional efficacy outcome measures were investigator-assessed progression-free survival (PFS) and objective response rate (ORR).

Median PFS was not statistically significant with immunotherapy; it was 5.1 months (95% CI, 4.7-6.2) in the durvalumab plus chemotherapy group and 5.4 months (95% CI, 4.8-6.2) in the chemotherapy alone group (HR, 0.78; 95% CI, 0.65-0.94).

The investigator-assessed ORR was 68% in the durvalumab plus chemotherapy group and 58% in the chemotherapy alone group.

The most common adverse reactions (≥ 20%) in patients with ES-SCLC were nausea, fatigue/asthenia, and alopecia, according to the FDA.

At ESMO, Paz-Ares reported that rates of serious adverse events (AEs) were comparable at 30.9% and 36.1% for the durvalumab plus EP group vs. EP alone, respectively; rates of AEs leading to discontinuation were identical in both groups at 9.4%. Unsurprisingly, immune-mediated AEs were higher at 19.6% in the durvalumab combination group vs. 2.6% in the EP alone group.

In this setting, durvalumab is administered prior to chemotherapy on the same day. The recommended durvalumab dose (when administered with etoposide and carboplatin or cisplatin) is 1,500 mg every 3 weeks prior to chemotherapy and then every 4 weeks as a single-agent maintenance therapy.

Durvalumab is already approved for metastatic non–small cell lung cancer in patients whose tumors have only spread in the chest, and is also approved for use in urothelial cancer.

This article first appeared on Medscape.com.

The US Food and Drug Administration has approved the immunotherapy durvalumab (Imfinzi, AstraZeneca) in combination with etoposide and either carboplatin or cisplatin as first-line treatment of patients with extensive-stage small cell lung cancer (ES-SCLC).

Durvalumab plus chemotherapy “can be considered a new standard in ES-SCLC,” said Myung-Ju Ahn, MD, Sungkyunkwan University, Seoul, South Korea, last year at the European Society of Medical Oncology (ESMO) annual meeting, where he discussed results from the phase 3 trial known as CASPIAN.

The new approval is based on efficacy and safety data from that trial, conducted in patients with previously untreated ES-SCLC. In the experimental group (n = 268), durvalumab plus etoposide and a platinum agent (EP) was followed by maintenance durvalumab, and in the control group (n = 269) patients received the EP regimen alone.

Median overall survival (OS) was 13 months in the durvalumab plus chemotherapy group compared with 10.3 months in the chemotherapy alone group (hazard ratio 0.73; 95% confidence interval, 0.59-0.91; P = .0047).

Reporting these results, trial investigator Luis Paz-Ares, MD, Hospital Universitario 12 de Octubre, Madrid, put the new survival benefit in the context of standard treatments at the ESMO meeting last year.

“Initial response rates to etoposide plus a platinum are high, but responses are not durable and patients treated with EP typically relapse within 6 months of starting treatment with a median OS of approximately 10 months,” he said.

In addition to the primary endpoint of OS, additional efficacy outcome measures were investigator-assessed progression-free survival (PFS) and objective response rate (ORR).

Median PFS was not statistically significant with immunotherapy; it was 5.1 months (95% CI, 4.7-6.2) in the durvalumab plus chemotherapy group and 5.4 months (95% CI, 4.8-6.2) in the chemotherapy alone group (HR, 0.78; 95% CI, 0.65-0.94).

The investigator-assessed ORR was 68% in the durvalumab plus chemotherapy group and 58% in the chemotherapy alone group.

The most common adverse reactions (≥ 20%) in patients with ES-SCLC were nausea, fatigue/asthenia, and alopecia, according to the FDA.

At ESMO, Paz-Ares reported that rates of serious adverse events (AEs) were comparable at 30.9% and 36.1% for the durvalumab plus EP group vs. EP alone, respectively; rates of AEs leading to discontinuation were identical in both groups at 9.4%. Unsurprisingly, immune-mediated AEs were higher at 19.6% in the durvalumab combination group vs. 2.6% in the EP alone group.

In this setting, durvalumab is administered prior to chemotherapy on the same day. The recommended durvalumab dose (when administered with etoposide and carboplatin or cisplatin) is 1,500 mg every 3 weeks prior to chemotherapy and then every 4 weeks as a single-agent maintenance therapy.

Durvalumab is already approved for metastatic non–small cell lung cancer in patients whose tumors have only spread in the chest, and is also approved for use in urothelial cancer.

This article first appeared on Medscape.com.

Among patients who undergo endobronchial ultrasound-guided transbronchial biopsy using a guide sheath (EBUS-GS-TBB) for diagnosing lung cancer, cavitation and low-density areas inside the target lesion on CT and stenosis of the responsible bronchus are risk factors for infection after the procedure, according to a study published in CHEST.

“Infectious complications after [transbronchial biopsy] constitute a serious clinical problem because they might delay the start of treatment or cause the intended treatment to be modified to a milder one,” said Tomohide Souma, MD, of the department of respiratory medicine at Fujita Health University in Toyoake, Japan, and colleagues. “The precise mechanism of such complications is still unclear, and effective prophylaxis procedures have not been established. ... Thus, it is very important to identify the risk factors for infectious complications after TBB if and when these complications are to be avoided.”

To evaluate potential risk factors for infectious complications after EBUS-GS-TBB in a large sample of patients, Dr. Souma and colleagues retrospectively studied the medical records of 1,045 consecutive patients (median age, 72; 68% male) who underwent EBUS-GS-TBB between January 2013 and December 2017 at Fujita Health University Hospital.

In all, 47 patients developed infections, a cumulative incidence of about 4.5%. Infections included pneumonia (51.1%), intratumoral infection (29.8%), and three cases each of lung abscess, pleurisy, and empyema. Three patients, two with empyema and one with lung abscess, died within 1 month before administration of anticancer treatment. “In total, more than 40% of patients with post–EBUS-GS-TBB infection were unable to receive preplanned anticancer treatment,” the researchers said.

On multivariate analysis, cavitation in the lesion (odds ratio, 3.63), low-density areas in the lesion (OR, 13.26), and bronchoscopic findings of responsible bronchus stenosis (OR, 7.82) were significantly associated with development of infections post biopsy.

An analysis that matched 89 patients who received prophylactic antibiotics with controls who did not receive prophylactic antibiotics did not find that prophylactic antibiotics significantly reduced the likelihood of post–EBUS-GS-TBB infection.

“Notably, three risk factors found in our study indicate that the inflammation-prone status of lesions may be the most important factor for developing post–EBUS-TBB infection,” Dr. Souma and colleagues said. “Although our study does not rebuff the role of antibiotics in postbronchoscopy infection therapy, clinicians should notify patients that post-TBB infection may occur despite the use of prophylactic antibiotics. We recommend that careful and frequent follow-up be applied to patients undergoing diagnostic EBUS-GS-TBB with reference to the risk factors identified in our study.”

A. Christine Argento, MD, FCCP, assistant professor of medicine and thoracic surgery and director of the interventional pulmonary fellowship program at Northwestern University, Chicago, noted that this is an important study on a topic that has not been well described in the past.

jremaly@mdedge.com

SOURCE: Souma T et al. CHEST. 2020 Mar 4. doi: 10.1016/j.chest.2020.02.025.

Among patients who undergo endobronchial ultrasound-guided transbronchial biopsy using a guide sheath (EBUS-GS-TBB) for diagnosing lung cancer, cavitation and low-density areas inside the target lesion on CT and stenosis of the responsible bronchus are risk factors for infection after the procedure, according to a study published in CHEST.

“Infectious complications after [transbronchial biopsy] constitute a serious clinical problem because they might delay the start of treatment or cause the intended treatment to be modified to a milder one,” said Tomohide Souma, MD, of the department of respiratory medicine at Fujita Health University in Toyoake, Japan, and colleagues. “The precise mechanism of such complications is still unclear, and effective prophylaxis procedures have not been established. ... Thus, it is very important to identify the risk factors for infectious complications after TBB if and when these complications are to be avoided.”

To evaluate potential risk factors for infectious complications after EBUS-GS-TBB in a large sample of patients, Dr. Souma and colleagues retrospectively studied the medical records of 1,045 consecutive patients (median age, 72; 68% male) who underwent EBUS-GS-TBB between January 2013 and December 2017 at Fujita Health University Hospital.

In all, 47 patients developed infections, a cumulative incidence of about 4.5%. Infections included pneumonia (51.1%), intratumoral infection (29.8%), and three cases each of lung abscess, pleurisy, and empyema. Three patients, two with empyema and one with lung abscess, died within 1 month before administration of anticancer treatment. “In total, more than 40% of patients with post–EBUS-GS-TBB infection were unable to receive preplanned anticancer treatment,” the researchers said.

On multivariate analysis, cavitation in the lesion (odds ratio, 3.63), low-density areas in the lesion (OR, 13.26), and bronchoscopic findings of responsible bronchus stenosis (OR, 7.82) were significantly associated with development of infections post biopsy.

An analysis that matched 89 patients who received prophylactic antibiotics with controls who did not receive prophylactic antibiotics did not find that prophylactic antibiotics significantly reduced the likelihood of post–EBUS-GS-TBB infection.

“Notably, three risk factors found in our study indicate that the inflammation-prone status of lesions may be the most important factor for developing post–EBUS-TBB infection,” Dr. Souma and colleagues said. “Although our study does not rebuff the role of antibiotics in postbronchoscopy infection therapy, clinicians should notify patients that post-TBB infection may occur despite the use of prophylactic antibiotics. We recommend that careful and frequent follow-up be applied to patients undergoing diagnostic EBUS-GS-TBB with reference to the risk factors identified in our study.”

A. Christine Argento, MD, FCCP, assistant professor of medicine and thoracic surgery and director of the interventional pulmonary fellowship program at Northwestern University, Chicago, noted that this is an important study on a topic that has not been well described in the past.

jremaly@mdedge.com

SOURCE: Souma T et al. CHEST. 2020 Mar 4. doi: 10.1016/j.chest.2020.02.025.

Among patients who undergo endobronchial ultrasound-guided transbronchial biopsy using a guide sheath (EBUS-GS-TBB) for diagnosing lung cancer, cavitation and low-density areas inside the target lesion on CT and stenosis of the responsible bronchus are risk factors for infection after the procedure, according to a study published in CHEST.

“Infectious complications after [transbronchial biopsy] constitute a serious clinical problem because they might delay the start of treatment or cause the intended treatment to be modified to a milder one,” said Tomohide Souma, MD, of the department of respiratory medicine at Fujita Health University in Toyoake, Japan, and colleagues. “The precise mechanism of such complications is still unclear, and effective prophylaxis procedures have not been established. ... Thus, it is very important to identify the risk factors for infectious complications after TBB if and when these complications are to be avoided.”

To evaluate potential risk factors for infectious complications after EBUS-GS-TBB in a large sample of patients, Dr. Souma and colleagues retrospectively studied the medical records of 1,045 consecutive patients (median age, 72; 68% male) who underwent EBUS-GS-TBB between January 2013 and December 2017 at Fujita Health University Hospital.

In all, 47 patients developed infections, a cumulative incidence of about 4.5%. Infections included pneumonia (51.1%), intratumoral infection (29.8%), and three cases each of lung abscess, pleurisy, and empyema. Three patients, two with empyema and one with lung abscess, died within 1 month before administration of anticancer treatment. “In total, more than 40% of patients with post–EBUS-GS-TBB infection were unable to receive preplanned anticancer treatment,” the researchers said.

On multivariate analysis, cavitation in the lesion (odds ratio, 3.63), low-density areas in the lesion (OR, 13.26), and bronchoscopic findings of responsible bronchus stenosis (OR, 7.82) were significantly associated with development of infections post biopsy.

An analysis that matched 89 patients who received prophylactic antibiotics with controls who did not receive prophylactic antibiotics did not find that prophylactic antibiotics significantly reduced the likelihood of post–EBUS-GS-TBB infection.

“Notably, three risk factors found in our study indicate that the inflammation-prone status of lesions may be the most important factor for developing post–EBUS-TBB infection,” Dr. Souma and colleagues said. “Although our study does not rebuff the role of antibiotics in postbronchoscopy infection therapy, clinicians should notify patients that post-TBB infection may occur despite the use of prophylactic antibiotics. We recommend that careful and frequent follow-up be applied to patients undergoing diagnostic EBUS-GS-TBB with reference to the risk factors identified in our study.”

A. Christine Argento, MD, FCCP, assistant professor of medicine and thoracic surgery and director of the interventional pulmonary fellowship program at Northwestern University, Chicago, noted that this is an important study on a topic that has not been well described in the past.

jremaly@mdedge.com

SOURCE: Souma T et al. CHEST. 2020 Mar 4. doi: 10.1016/j.chest.2020.02.025.

Cancer surgeries may need to be delayed as hospitals are forced to allocate resources to a surge of COVID-19 patients, says the American College of Surgeons, as it issues a new set of recommendations in reaction to the crisis.

Most surgeons have already curtailed or have ceased to perform elective operations, the ACS notes, and recommends that surgeons continue to do so in order to preserve the necessary resources for care of critically ill patients during the COVID-19 pandemic. The new clinical guidance for elective surgical case triage during the pandemic includes recommendations for cancer surgery as well as for procedures that are specific to certain cancer types.

“These triage guidelines and joint recommendations are being issued as we appear to be entering a new phase of the COVID-19 pandemic with more hospitals facing a potential push beyond their resources to care for critically ill patients,” commented ACS Executive Director David B. Hoyt, MD, in a statement.

“ACS will continue to monitor the landscape for surgical care but we feel this guidance document provides a good foundation for surgeons to begin enacting these triage recommendations today to help them make the best decisions possible for their patients during COVID-19,” he said.

For cancer surgery, which is often not elective but essential to treatment, ACS has issued general guidance for triaging patients, taking into account the acuity of the local COVID-19 situation.

First, decisions about whether to proceed with elective surgeries must consider the available resources of local facilities. The parties responsible for preparing the facility to manage coronavirus patients should be sharing information at regular intervals about constraints on local resources, especially personal protective equipment (PPE), which is running low in many jurisdictions. For example, if an elective case has a high likelihood of needing postoperative ICU care, it is imperative to balance the risk of delay against the need of availability for patients with COVID-19.

Second, cancer care coordination should use virtual technologies as much as possible, and facilities with tumor boards may find it helpful to locate multidisciplinary experts by virtual means, to assist with decision making and establishing triage criteria.

Three Phases of Pandemic

The ACS has also organized decision making into three phases that reflect the acuity of the local COVID-19 situation:

• Phase I. Semi-Urgent Setting (Preparation Phase) – few COVID-19 patients, hospital resources not exhausted, institution still has ICU ventilator capacity and COVID-19 trajectory not in rapid escalation phase
• Phase II. Urgent Setting – many COVID-19 patients, ICU and ventilator capacity limited, operating room supplies limited
• Phase III. Hospital resources are all routed to COVID-19 patients, no ventilator or ICU capacity, operating room supplies exhausted; patients in whom death is likely within hours if surgery is deferred

Breast Cancer Surgery

The ACS also issued specific guidance for several tumor types, including guidance for breast cancer surgery.

For phase I, surgery should be restricted to patients who are likely to experience compromised survival if it is not performed within next 3 months. This includes patients completing neoadjuvant treatment, those with clinical stage T2 or N1 ERpos/PRpos/HER2-negative tumors, patients with triple negative or HER2-positive tumors, discordant biopsies that are likely to be malignant, and removal of a recurrent lesion.

Phase II would be restricted to patients whose survival is threatened if surgery is not performed within the next few days. These would include incision and drainage of breast abscess, evacuating a hematoma, revision of an ischemic mastectomy flap, and revascularization/revision of an autologous tissue flap (autologous reconstruction should be deferred).

In Phase III, surgical procedures would be restricted to patients who may not survive if surgery is not performed within a few hours. This includes incision and drainage of breast abscess, evacuation of a hematoma, revision of an ischemic mastectomy flap, and revascularization/revision of an autologous tissue flap (autologous reconstruction should be deferred).

Colorectal Cancer Surgery

Guidance for colorectal cancer surgery is also split into the three phases of the pandemic.

Phase I would include cases needing surgical intervention as soon as feasible, while recognizing that the status of each hospital is likely to evolve over the next week or two. These patients would include those with nearly obstructing colon cancer or rectal cancer; cancers that require frequent transfusions; asymptomatic colon cancers; rectal cancers that do not respond to neoadjuvant chemoradiation; malignancies with a risk of local perforation and sepsis; and those with early stage rectal cancers that are not candidates for adjuvant therapy.

Phase II comprises patients needing surgery as soon as feasible, but recognizing that hospital status is likely to progress over the next few days. These cases include patients with a nearly obstructing colon cancer where stenting is not an option; those with nearly obstructing rectal cancer (should be diverted); cancers with high (inpatient) transfusion requirements; and cancers with pending evidence of local perforation and sepsis.

All colorectal procedures typically scheduled as routine should be delayed.

In Phase III, if the status of the facility is likely to progress within hours, the only surgery that should be performed would be for perforated, obstructed, or actively bleeding (inpatient transfusion dependent) cancers or those with sepsis. All other surgeries should be deferred.

Thoracic Cancer Surgery

Thoracic cancer surgery guidelines follow those for breast cancer. Phase I should be restricted to patients whose survival may be impacted if surgery is not performed within next 3 months. These include:

• Cases with solid or predominantly solid (>50%) lung cancer or presumed lung cancer (>2 cm), clinical node negative
• Node positive lung cancer
• Post-induction therapy cancer
• Esophageal cancer T1b or greater
• Chest wall tumors that are potentially aggressive and not manageable by alternative means
• Stenting for obstructing esophageal tumor
• Staging to start treatment (mediastinoscopy, diagnostic VATS for pleural dissemination)
• Symptomatic mediastinal tumors
• Patients who are enrolled in therapeutic clinical trials.

Phase II would permit surgery if survival will be impacted by a delay of a few days. These cases would include nonseptic perforated cancer of esophagus, a tumor-associated infection, and management of surgical complications in a hemodynamically stable patient.

All thoracic procedures considered to be routine/elective would be deferred.

Phase III restricts surgery to patients whose survival will be compromised if they do not undergo surgery within the next few hours. This group would include perforated cancer of esophagus in a septic patient, a patient with a threatened airway, sepsis associated with the cancer, and management of surgical complications in an unstable patient  (active bleeding that requires surgery, dehiscence of airway, anastomotic leak with sepsis).

All other cases would be deferred.

Other Cancer Types

Although the ACS doesn’t have specific guidelines for all cancer types, a few are included in their general recommendations for the specialty.

For gynecologic surgeries, ACS lists cancer or suspected cancer as indications where significantly delayed surgery could cause “significant harm.”

Delays, in general, are not recommended for neurosurgery, which would include brain cancers. In pediatrics, most cancer surgery is considered “urgent,” where a delay of days to weeks could prove detrimental to the patient. This would comprise all solid tumors, including the initial biopsy and resection following neoadjuvant therapy.
 

This article first appeared on Medscape.com.

Cancer surgeries may need to be delayed as hospitals are forced to allocate resources to a surge of COVID-19 patients, says the American College of Surgeons, as it issues a new set of recommendations in reaction to the crisis.

Most surgeons have already curtailed or have ceased to perform elective operations, the ACS notes, and recommends that surgeons continue to do so in order to preserve the necessary resources for care of critically ill patients during the COVID-19 pandemic. The new clinical guidance for elective surgical case triage during the pandemic includes recommendations for cancer surgery as well as for procedures that are specific to certain cancer types.

“These triage guidelines and joint recommendations are being issued as we appear to be entering a new phase of the COVID-19 pandemic with more hospitals facing a potential push beyond their resources to care for critically ill patients,” commented ACS Executive Director David B. Hoyt, MD, in a statement.

“ACS will continue to monitor the landscape for surgical care but we feel this guidance document provides a good foundation for surgeons to begin enacting these triage recommendations today to help them make the best decisions possible for their patients during COVID-19,” he said.

For cancer surgery, which is often not elective but essential to treatment, ACS has issued general guidance for triaging patients, taking into account the acuity of the local COVID-19 situation.

First, decisions about whether to proceed with elective surgeries must consider the available resources of local facilities. The parties responsible for preparing the facility to manage coronavirus patients should be sharing information at regular intervals about constraints on local resources, especially personal protective equipment (PPE), which is running low in many jurisdictions. For example, if an elective case has a high likelihood of needing postoperative ICU care, it is imperative to balance the risk of delay against the need of availability for patients with COVID-19.

Second, cancer care coordination should use virtual technologies as much as possible, and facilities with tumor boards may find it helpful to locate multidisciplinary experts by virtual means, to assist with decision making and establishing triage criteria.

Three Phases of Pandemic

The ACS has also organized decision making into three phases that reflect the acuity of the local COVID-19 situation:

• Phase I. Semi-Urgent Setting (Preparation Phase) – few COVID-19 patients, hospital resources not exhausted, institution still has ICU ventilator capacity and COVID-19 trajectory not in rapid escalation phase
• Phase II. Urgent Setting – many COVID-19 patients, ICU and ventilator capacity limited, operating room supplies limited
• Phase III. Hospital resources are all routed to COVID-19 patients, no ventilator or ICU capacity, operating room supplies exhausted; patients in whom death is likely within hours if surgery is deferred

Breast Cancer Surgery

The ACS also issued specific guidance for several tumor types, including guidance for breast cancer surgery.

For phase I, surgery should be restricted to patients who are likely to experience compromised survival if it is not performed within next 3 months. This includes patients completing neoadjuvant treatment, those with clinical stage T2 or N1 ERpos/PRpos/HER2-negative tumors, patients with triple negative or HER2-positive tumors, discordant biopsies that are likely to be malignant, and removal of a recurrent lesion.

Phase II would be restricted to patients whose survival is threatened if surgery is not performed within the next few days. These would include incision and drainage of breast abscess, evacuating a hematoma, revision of an ischemic mastectomy flap, and revascularization/revision of an autologous tissue flap (autologous reconstruction should be deferred).

In Phase III, surgical procedures would be restricted to patients who may not survive if surgery is not performed within a few hours. This includes incision and drainage of breast abscess, evacuation of a hematoma, revision of an ischemic mastectomy flap, and revascularization/revision of an autologous tissue flap (autologous reconstruction should be deferred).

Colorectal Cancer Surgery

Guidance for colorectal cancer surgery is also split into the three phases of the pandemic.

Phase I would include cases needing surgical intervention as soon as feasible, while recognizing that the status of each hospital is likely to evolve over the next week or two. These patients would include those with nearly obstructing colon cancer or rectal cancer; cancers that require frequent transfusions; asymptomatic colon cancers; rectal cancers that do not respond to neoadjuvant chemoradiation; malignancies with a risk of local perforation and sepsis; and those with early stage rectal cancers that are not candidates for adjuvant therapy.

Phase II comprises patients needing surgery as soon as feasible, but recognizing that hospital status is likely to progress over the next few days. These cases include patients with a nearly obstructing colon cancer where stenting is not an option; those with nearly obstructing rectal cancer (should be diverted); cancers with high (inpatient) transfusion requirements; and cancers with pending evidence of local perforation and sepsis.

All colorectal procedures typically scheduled as routine should be delayed.

In Phase III, if the status of the facility is likely to progress within hours, the only surgery that should be performed would be for perforated, obstructed, or actively bleeding (inpatient transfusion dependent) cancers or those with sepsis. All other surgeries should be deferred.

Thoracic Cancer Surgery

Thoracic cancer surgery guidelines follow those for breast cancer. Phase I should be restricted to patients whose survival may be impacted if surgery is not performed within next 3 months. These include:

• Cases with solid or predominantly solid (>50%) lung cancer or presumed lung cancer (>2 cm), clinical node negative
• Node positive lung cancer
• Post-induction therapy cancer
• Esophageal cancer T1b or greater
• Chest wall tumors that are potentially aggressive and not manageable by alternative means
• Stenting for obstructing esophageal tumor
• Staging to start treatment (mediastinoscopy, diagnostic VATS for pleural dissemination)
• Symptomatic mediastinal tumors
• Patients who are enrolled in therapeutic clinical trials.

Phase II would permit surgery if survival will be impacted by a delay of a few days. These cases would include nonseptic perforated cancer of esophagus, a tumor-associated infection, and management of surgical complications in a hemodynamically stable patient.

All thoracic procedures considered to be routine/elective would be deferred.

Phase III restricts surgery to patients whose survival will be compromised if they do not undergo surgery within the next few hours. This group would include perforated cancer of esophagus in a septic patient, a patient with a threatened airway, sepsis associated with the cancer, and management of surgical complications in an unstable patient  (active bleeding that requires surgery, dehiscence of airway, anastomotic leak with sepsis).

All other cases would be deferred.

Other Cancer Types

Although the ACS doesn’t have specific guidelines for all cancer types, a few are included in their general recommendations for the specialty.

For gynecologic surgeries, ACS lists cancer or suspected cancer as indications where significantly delayed surgery could cause “significant harm.”

Delays, in general, are not recommended for neurosurgery, which would include brain cancers. In pediatrics, most cancer surgery is considered “urgent,” where a delay of days to weeks could prove detrimental to the patient. This would comprise all solid tumors, including the initial biopsy and resection following neoadjuvant therapy.
 

This article first appeared on Medscape.com.

Cancer surgeries may need to be delayed as hospitals are forced to allocate resources to a surge of COVID-19 patients, says the American College of Surgeons, as it issues a new set of recommendations in reaction to the crisis.

Most surgeons have already curtailed or have ceased to perform elective operations, the ACS notes, and recommends that surgeons continue to do so in order to preserve the necessary resources for care of critically ill patients during the COVID-19 pandemic. The new clinical guidance for elective surgical case triage during the pandemic includes recommendations for cancer surgery as well as for procedures that are specific to certain cancer types.

“These triage guidelines and joint recommendations are being issued as we appear to be entering a new phase of the COVID-19 pandemic with more hospitals facing a potential push beyond their resources to care for critically ill patients,” commented ACS Executive Director David B. Hoyt, MD, in a statement.

“ACS will continue to monitor the landscape for surgical care but we feel this guidance document provides a good foundation for surgeons to begin enacting these triage recommendations today to help them make the best decisions possible for their patients during COVID-19,” he said.

For cancer surgery, which is often not elective but essential to treatment, ACS has issued general guidance for triaging patients, taking into account the acuity of the local COVID-19 situation.

First, decisions about whether to proceed with elective surgeries must consider the available resources of local facilities. The parties responsible for preparing the facility to manage coronavirus patients should be sharing information at regular intervals about constraints on local resources, especially personal protective equipment (PPE), which is running low in many jurisdictions. For example, if an elective case has a high likelihood of needing postoperative ICU care, it is imperative to balance the risk of delay against the need of availability for patients with COVID-19.

Second, cancer care coordination should use virtual technologies as much as possible, and facilities with tumor boards may find it helpful to locate multidisciplinary experts by virtual means, to assist with decision making and establishing triage criteria.

Three Phases of Pandemic

The ACS has also organized decision making into three phases that reflect the acuity of the local COVID-19 situation:

• Phase I. Semi-Urgent Setting (Preparation Phase) – few COVID-19 patients, hospital resources not exhausted, institution still has ICU ventilator capacity and COVID-19 trajectory not in rapid escalation phase
• Phase II. Urgent Setting – many COVID-19 patients, ICU and ventilator capacity limited, operating room supplies limited
• Phase III. Hospital resources are all routed to COVID-19 patients, no ventilator or ICU capacity, operating room supplies exhausted; patients in whom death is likely within hours if surgery is deferred

Breast Cancer Surgery

The ACS also issued specific guidance for several tumor types, including guidance for breast cancer surgery.

For phase I, surgery should be restricted to patients who are likely to experience compromised survival if it is not performed within next 3 months. This includes patients completing neoadjuvant treatment, those with clinical stage T2 or N1 ERpos/PRpos/HER2-negative tumors, patients with triple negative or HER2-positive tumors, discordant biopsies that are likely to be malignant, and removal of a recurrent lesion.

Phase II would be restricted to patients whose survival is threatened if surgery is not performed within the next few days. These would include incision and drainage of breast abscess, evacuating a hematoma, revision of an ischemic mastectomy flap, and revascularization/revision of an autologous tissue flap (autologous reconstruction should be deferred).

In Phase III, surgical procedures would be restricted to patients who may not survive if surgery is not performed within a few hours. This includes incision and drainage of breast abscess, evacuation of a hematoma, revision of an ischemic mastectomy flap, and revascularization/revision of an autologous tissue flap (autologous reconstruction should be deferred).

Colorectal Cancer Surgery

Guidance for colorectal cancer surgery is also split into the three phases of the pandemic.

Phase I would include cases needing surgical intervention as soon as feasible, while recognizing that the status of each hospital is likely to evolve over the next week or two. These patients would include those with nearly obstructing colon cancer or rectal cancer; cancers that require frequent transfusions; asymptomatic colon cancers; rectal cancers that do not respond to neoadjuvant chemoradiation; malignancies with a risk of local perforation and sepsis; and those with early stage rectal cancers that are not candidates for adjuvant therapy.

Phase II comprises patients needing surgery as soon as feasible, but recognizing that hospital status is likely to progress over the next few days. These cases include patients with a nearly obstructing colon cancer where stenting is not an option; those with nearly obstructing rectal cancer (should be diverted); cancers with high (inpatient) transfusion requirements; and cancers with pending evidence of local perforation and sepsis.

All colorectal procedures typically scheduled as routine should be delayed.

In Phase III, if the status of the facility is likely to progress within hours, the only surgery that should be performed would be for perforated, obstructed, or actively bleeding (inpatient transfusion dependent) cancers or those with sepsis. All other surgeries should be deferred.

Thoracic Cancer Surgery

Thoracic cancer surgery guidelines follow those for breast cancer. Phase I should be restricted to patients whose survival may be impacted if surgery is not performed within next 3 months. These include:

• Cases with solid or predominantly solid (>50%) lung cancer or presumed lung cancer (>2 cm), clinical node negative
• Node positive lung cancer
• Post-induction therapy cancer
• Esophageal cancer T1b or greater
• Chest wall tumors that are potentially aggressive and not manageable by alternative means
• Stenting for obstructing esophageal tumor
• Staging to start treatment (mediastinoscopy, diagnostic VATS for pleural dissemination)
• Symptomatic mediastinal tumors
• Patients who are enrolled in therapeutic clinical trials.

Phase II would permit surgery if survival will be impacted by a delay of a few days. These cases would include nonseptic perforated cancer of esophagus, a tumor-associated infection, and management of surgical complications in a hemodynamically stable patient.

All thoracic procedures considered to be routine/elective would be deferred.

Phase III restricts surgery to patients whose survival will be compromised if they do not undergo surgery within the next few hours. This group would include perforated cancer of esophagus in a septic patient, a patient with a threatened airway, sepsis associated with the cancer, and management of surgical complications in an unstable patient  (active bleeding that requires surgery, dehiscence of airway, anastomotic leak with sepsis).

All other cases would be deferred.

Other Cancer Types

Although the ACS doesn’t have specific guidelines for all cancer types, a few are included in their general recommendations for the specialty.

For gynecologic surgeries, ACS lists cancer or suspected cancer as indications where significantly delayed surgery could cause “significant harm.”

Delays, in general, are not recommended for neurosurgery, which would include brain cancers. In pediatrics, most cancer surgery is considered “urgent,” where a delay of days to weeks could prove detrimental to the patient. This would comprise all solid tumors, including the initial biopsy and resection following neoadjuvant therapy.
 

This article first appeared on Medscape.com.

I have no knowledge of, or experience with, managing a cancer patient during a pandemic. However, from the published and otherwise shared experience of others, we should not allow ourselves to underestimate the voracity of the coronavirus pandemic on our patients, communities, and health care systems.

Data from China suggest cancer patients infected with SARS-CoV-2 face a 3.5 times higher risk of mechanical ventilation, intensive care unit admission, or death, compared with infected patients without cancer (Lancet Oncol 2020;21:335-7).

Health care workers in Seattle have also shared their experiences battling coronavirus infections in cancer patients (J Natl Compr Canc Netw. 2020 Mar 20. doi: 10.6004/jnccn.2020.7560). Masumi Ueda, MD, of Seattle Cancer Care Alliance, and colleagues reviewed their decisions in multiple domains over a 7-week period, during which the state of Washington went from a single case of SARS-CoV-2 infection to nearly 650 cases and 40 deaths.
 

Making tough treatment decisions

Dr. Ueda and colleagues contrasted their customary resource-rich, innovation-oriented, cancer-combatting environment with their current circumstance, in which they must prioritize treatment for patients for whom the risk-reward balance has tilted substantially toward “risk.”

The authors noted that their most difficult decisions were those regarding delay of cancer treatment. They suggested that plans for potentially curative adjuvant therapy should likely proceed, but, for patients with metastatic disease, the equation is more nuanced.

In some cases, treatment should be delayed or interrupted with recognition of how that could result in worsening performance status and admission for symptom palliation, further stressing inpatient resources.

The authors suggested scenarios for prioritizing cancer surgery. For example, several months of systemic therapy (ideally, low-risk systemic therapy such as hormone therapy for breast or prostate cancer) and surgical delay may be worthwhile, without compromising patient care.

Patients with aggressive hematologic malignancy requiring urgent systemic treatment (potentially stem cell transplantation and cellular immunotherapies) should be treated promptly. However, even in those cases, opportunities should be sought to lessen immunosuppression and transition care as quickly as possible to the outpatient clinic, according to guidelines from the American Society of Transplantation and Cellular Therapy.
 

See one, do one, teach one

Rendering patient care during a pandemic would be unique for me. However, I, like all physicians, am familiar with feelings of inadequacy at times of professional challenge. On countless occasions, I have started my day or walked into a patient’s room wondering whether I will have the fortitude, knowledge, creativity, or help I need to get through that day or make that patient “better” by any definition of that word.

We all know the formula: “Work hard. Make evidence-based, personalized decisions for those who have entrusted their care to us. Learn from those encounters. Teach from our knowledge and experience – that is, ‘See one, do one, teach one.’ ”

The Seattle oncologists are living the lives of first responders and deserve our admiration for putting pen to paper so we can learn from their considerable, relevant experience.

Similar admiration is due to Giuseppe Curigliano, MD, of the European Institute of Oncology in Milan. In the ASCO Daily News, Dr. Curigliano described an epidemic that, within 3 weeks, overloaded the health care system across northern Italy.

Hospitalization was needed for over 60% of infected patients, and nearly 15% of those patients needed intensive care unit services for respiratory distress. The Italians centralized oncology care in specialized hubs, with spokes of institutions working in parallel to provide cancer-specific care in a COVID-free environment.

To build upon cancer-specific information from Italy and other areas hard-hit by COVID-19, more than 30 cancer centers have joined together to form the COVID-19 and Cancer Consortium. The consortium’s website hosts a survey designed to “capture details related to cancer patients presumed to have COVID-19.”
 

Calculating deaths and long-term consequences for cancer care delivery

It is proper that the authors from China, Italy, and Seattle did not focus attention on the case fatality rate from the COVID-19 pandemic among cancer patients. To say the least, it would be complicated to tally the direct mortality – either overall or in clinically important subsets of patients, including country-specific cohorts.

What we know from published reports is that, in Italy, cancer patients account for about 20% of deaths from coronavirus. In China, the case-fatality rate for patients with cancer was 5.6% (JAMA. 2020 Feb 24. doi: 10.1001/jama.2020.2648).

However, we know nothing about the indirect death toll from malignancy (without coronavirus infection) that was untreated or managed less than optimally because of personnel and physical resources that were diverted to COVID-19–associated cases.

Similarly, we cannot begin to estimate indirect consequences of the pandemic to oncology practices, such as accelerated burnout and posttraumatic stress disorder, as well as the long-range effects of economic turmoil on patients, health care workers, and provider organizations.
 

What happens to cancer trials?

From China, Italy, and Seattle, thus far, there is little information about how the pandemic will affect the vital clinical research endeavor. The Seattle physicians did say they plan to enroll patients on clinical trials only when the trial offers a high chance of benefiting the patient over standard therapy alone.

Fortunately, the National Institutes of Health and Food and Drug Administration have released guidance documents related to clinical trials.

The National Cancer Institute (NCI) has also released guidance documents (March 13 guidance; March 23 guidance) for patients on clinical trials supported by the NCI Cancer Therapy Evaluation Program (CTEP) and the NCI Community Oncology Research Program (NCORP).

CTEP and NCORP are making reasonable accommodations to suspend monitoring visits and audits, allow tele–follow-up visits for patients, and permit local physicians to provide care for patients on study. In addition, with appropriate procedural adherence and documentation, CTEP and NCORP will allow oral investigational medicines to be mailed directly to patients’ homes.

Planned NCI National Clinical Trials Network meetings will be conducted via remote access webinars, conference calls, and similar technology. These adjustments – and probably many more to come – are geared toward facilitating ongoing care to proceed safely and with minimal risk for patients currently receiving investigational therapies and for the sites and investigators engaged in those studies.

Each of us has probably faced a personal “defining professional moment,” when we had to utilize every skill in our arsenal and examine the motivations that led us to a career in oncology. However, it is clear from the forgoing clinical and research processes and guidelines that the COVID-19 pandemic is such a defining professional moment for each of us, in every community we serve.

Critical junctures like this cause more rapid behavior change and innovation than the slow-moving pace that characterizes our idealized preferences. As oncologists who embrace new data and behavioral change, we stand to learn processes that will facilitate more perfected systems of care than the one that preceded this unprecedented crisis, promote more efficient sharing of high-quality information, and improve the outcome for our future patients.


Dr. Lyss was an oncologist and researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

I have no knowledge of, or experience with, managing a cancer patient during a pandemic. However, from the published and otherwise shared experience of others, we should not allow ourselves to underestimate the voracity of the coronavirus pandemic on our patients, communities, and health care systems.

Data from China suggest cancer patients infected with SARS-CoV-2 face a 3.5 times higher risk of mechanical ventilation, intensive care unit admission, or death, compared with infected patients without cancer (Lancet Oncol 2020;21:335-7).

Health care workers in Seattle have also shared their experiences battling coronavirus infections in cancer patients (J Natl Compr Canc Netw. 2020 Mar 20. doi: 10.6004/jnccn.2020.7560). Masumi Ueda, MD, of Seattle Cancer Care Alliance, and colleagues reviewed their decisions in multiple domains over a 7-week period, during which the state of Washington went from a single case of SARS-CoV-2 infection to nearly 650 cases and 40 deaths.
 

Making tough treatment decisions

Dr. Ueda and colleagues contrasted their customary resource-rich, innovation-oriented, cancer-combatting environment with their current circumstance, in which they must prioritize treatment for patients for whom the risk-reward balance has tilted substantially toward “risk.”

The authors noted that their most difficult decisions were those regarding delay of cancer treatment. They suggested that plans for potentially curative adjuvant therapy should likely proceed, but, for patients with metastatic disease, the equation is more nuanced.

In some cases, treatment should be delayed or interrupted with recognition of how that could result in worsening performance status and admission for symptom palliation, further stressing inpatient resources.

The authors suggested scenarios for prioritizing cancer surgery. For example, several months of systemic therapy (ideally, low-risk systemic therapy such as hormone therapy for breast or prostate cancer) and surgical delay may be worthwhile, without compromising patient care.

Patients with aggressive hematologic malignancy requiring urgent systemic treatment (potentially stem cell transplantation and cellular immunotherapies) should be treated promptly. However, even in those cases, opportunities should be sought to lessen immunosuppression and transition care as quickly as possible to the outpatient clinic, according to guidelines from the American Society of Transplantation and Cellular Therapy.
 

See one, do one, teach one

Rendering patient care during a pandemic would be unique for me. However, I, like all physicians, am familiar with feelings of inadequacy at times of professional challenge. On countless occasions, I have started my day or walked into a patient’s room wondering whether I will have the fortitude, knowledge, creativity, or help I need to get through that day or make that patient “better” by any definition of that word.

We all know the formula: “Work hard. Make evidence-based, personalized decisions for those who have entrusted their care to us. Learn from those encounters. Teach from our knowledge and experience – that is, ‘See one, do one, teach one.’ ”

The Seattle oncologists are living the lives of first responders and deserve our admiration for putting pen to paper so we can learn from their considerable, relevant experience.

Similar admiration is due to Giuseppe Curigliano, MD, of the European Institute of Oncology in Milan. In the ASCO Daily News, Dr. Curigliano described an epidemic that, within 3 weeks, overloaded the health care system across northern Italy.

Hospitalization was needed for over 60% of infected patients, and nearly 15% of those patients needed intensive care unit services for respiratory distress. The Italians centralized oncology care in specialized hubs, with spokes of institutions working in parallel to provide cancer-specific care in a COVID-free environment.

To build upon cancer-specific information from Italy and other areas hard-hit by COVID-19, more than 30 cancer centers have joined together to form the COVID-19 and Cancer Consortium. The consortium’s website hosts a survey designed to “capture details related to cancer patients presumed to have COVID-19.”
 

Calculating deaths and long-term consequences for cancer care delivery

It is proper that the authors from China, Italy, and Seattle did not focus attention on the case fatality rate from the COVID-19 pandemic among cancer patients. To say the least, it would be complicated to tally the direct mortality – either overall or in clinically important subsets of patients, including country-specific cohorts.

What we know from published reports is that, in Italy, cancer patients account for about 20% of deaths from coronavirus. In China, the case-fatality rate for patients with cancer was 5.6% (JAMA. 2020 Feb 24. doi: 10.1001/jama.2020.2648).

However, we know nothing about the indirect death toll from malignancy (without coronavirus infection) that was untreated or managed less than optimally because of personnel and physical resources that were diverted to COVID-19–associated cases.

Similarly, we cannot begin to estimate indirect consequences of the pandemic to oncology practices, such as accelerated burnout and posttraumatic stress disorder, as well as the long-range effects of economic turmoil on patients, health care workers, and provider organizations.
 

What happens to cancer trials?

From China, Italy, and Seattle, thus far, there is little information about how the pandemic will affect the vital clinical research endeavor. The Seattle physicians did say they plan to enroll patients on clinical trials only when the trial offers a high chance of benefiting the patient over standard therapy alone.

Fortunately, the National Institutes of Health and Food and Drug Administration have released guidance documents related to clinical trials.

The National Cancer Institute (NCI) has also released guidance documents (March 13 guidance; March 23 guidance) for patients on clinical trials supported by the NCI Cancer Therapy Evaluation Program (CTEP) and the NCI Community Oncology Research Program (NCORP).

CTEP and NCORP are making reasonable accommodations to suspend monitoring visits and audits, allow tele–follow-up visits for patients, and permit local physicians to provide care for patients on study. In addition, with appropriate procedural adherence and documentation, CTEP and NCORP will allow oral investigational medicines to be mailed directly to patients’ homes.

Planned NCI National Clinical Trials Network meetings will be conducted via remote access webinars, conference calls, and similar technology. These adjustments – and probably many more to come – are geared toward facilitating ongoing care to proceed safely and with minimal risk for patients currently receiving investigational therapies and for the sites and investigators engaged in those studies.

Each of us has probably faced a personal “defining professional moment,” when we had to utilize every skill in our arsenal and examine the motivations that led us to a career in oncology. However, it is clear from the forgoing clinical and research processes and guidelines that the COVID-19 pandemic is such a defining professional moment for each of us, in every community we serve.

Critical junctures like this cause more rapid behavior change and innovation than the slow-moving pace that characterizes our idealized preferences. As oncologists who embrace new data and behavioral change, we stand to learn processes that will facilitate more perfected systems of care than the one that preceded this unprecedented crisis, promote more efficient sharing of high-quality information, and improve the outcome for our future patients.


Dr. Lyss was an oncologist and researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

I have no knowledge of, or experience with, managing a cancer patient during a pandemic. However, from the published and otherwise shared experience of others, we should not allow ourselves to underestimate the voracity of the coronavirus pandemic on our patients, communities, and health care systems.

Data from China suggest cancer patients infected with SARS-CoV-2 face a 3.5 times higher risk of mechanical ventilation, intensive care unit admission, or death, compared with infected patients without cancer (Lancet Oncol 2020;21:335-7).

Health care workers in Seattle have also shared their experiences battling coronavirus infections in cancer patients (J Natl Compr Canc Netw. 2020 Mar 20. doi: 10.6004/jnccn.2020.7560). Masumi Ueda, MD, of Seattle Cancer Care Alliance, and colleagues reviewed their decisions in multiple domains over a 7-week period, during which the state of Washington went from a single case of SARS-CoV-2 infection to nearly 650 cases and 40 deaths.
 

Making tough treatment decisions

Dr. Ueda and colleagues contrasted their customary resource-rich, innovation-oriented, cancer-combatting environment with their current circumstance, in which they must prioritize treatment for patients for whom the risk-reward balance has tilted substantially toward “risk.”

The authors noted that their most difficult decisions were those regarding delay of cancer treatment. They suggested that plans for potentially curative adjuvant therapy should likely proceed, but, for patients with metastatic disease, the equation is more nuanced.

In some cases, treatment should be delayed or interrupted with recognition of how that could result in worsening performance status and admission for symptom palliation, further stressing inpatient resources.

The authors suggested scenarios for prioritizing cancer surgery. For example, several months of systemic therapy (ideally, low-risk systemic therapy such as hormone therapy for breast or prostate cancer) and surgical delay may be worthwhile, without compromising patient care.

Patients with aggressive hematologic malignancy requiring urgent systemic treatment (potentially stem cell transplantation and cellular immunotherapies) should be treated promptly. However, even in those cases, opportunities should be sought to lessen immunosuppression and transition care as quickly as possible to the outpatient clinic, according to guidelines from the American Society of Transplantation and Cellular Therapy.
 

See one, do one, teach one

Rendering patient care during a pandemic would be unique for me. However, I, like all physicians, am familiar with feelings of inadequacy at times of professional challenge. On countless occasions, I have started my day or walked into a patient’s room wondering whether I will have the fortitude, knowledge, creativity, or help I need to get through that day or make that patient “better” by any definition of that word.

We all know the formula: “Work hard. Make evidence-based, personalized decisions for those who have entrusted their care to us. Learn from those encounters. Teach from our knowledge and experience – that is, ‘See one, do one, teach one.’ ”

The Seattle oncologists are living the lives of first responders and deserve our admiration for putting pen to paper so we can learn from their considerable, relevant experience.

Similar admiration is due to Giuseppe Curigliano, MD, of the European Institute of Oncology in Milan. In the ASCO Daily News, Dr. Curigliano described an epidemic that, within 3 weeks, overloaded the health care system across northern Italy.

Hospitalization was needed for over 60% of infected patients, and nearly 15% of those patients needed intensive care unit services for respiratory distress. The Italians centralized oncology care in specialized hubs, with spokes of institutions working in parallel to provide cancer-specific care in a COVID-free environment.

To build upon cancer-specific information from Italy and other areas hard-hit by COVID-19, more than 30 cancer centers have joined together to form the COVID-19 and Cancer Consortium. The consortium’s website hosts a survey designed to “capture details related to cancer patients presumed to have COVID-19.”
 

Calculating deaths and long-term consequences for cancer care delivery

It is proper that the authors from China, Italy, and Seattle did not focus attention on the case fatality rate from the COVID-19 pandemic among cancer patients. To say the least, it would be complicated to tally the direct mortality – either overall or in clinically important subsets of patients, including country-specific cohorts.

What we know from published reports is that, in Italy, cancer patients account for about 20% of deaths from coronavirus. In China, the case-fatality rate for patients with cancer was 5.6% (JAMA. 2020 Feb 24. doi: 10.1001/jama.2020.2648).

However, we know nothing about the indirect death toll from malignancy (without coronavirus infection) that was untreated or managed less than optimally because of personnel and physical resources that were diverted to COVID-19–associated cases.

Similarly, we cannot begin to estimate indirect consequences of the pandemic to oncology practices, such as accelerated burnout and posttraumatic stress disorder, as well as the long-range effects of economic turmoil on patients, health care workers, and provider organizations.
 

What happens to cancer trials?

From China, Italy, and Seattle, thus far, there is little information about how the pandemic will affect the vital clinical research endeavor. The Seattle physicians did say they plan to enroll patients on clinical trials only when the trial offers a high chance of benefiting the patient over standard therapy alone.

Fortunately, the National Institutes of Health and Food and Drug Administration have released guidance documents related to clinical trials.

The National Cancer Institute (NCI) has also released guidance documents (March 13 guidance; March 23 guidance) for patients on clinical trials supported by the NCI Cancer Therapy Evaluation Program (CTEP) and the NCI Community Oncology Research Program (NCORP).

CTEP and NCORP are making reasonable accommodations to suspend monitoring visits and audits, allow tele–follow-up visits for patients, and permit local physicians to provide care for patients on study. In addition, with appropriate procedural adherence and documentation, CTEP and NCORP will allow oral investigational medicines to be mailed directly to patients’ homes.

Planned NCI National Clinical Trials Network meetings will be conducted via remote access webinars, conference calls, and similar technology. These adjustments – and probably many more to come – are geared toward facilitating ongoing care to proceed safely and with minimal risk for patients currently receiving investigational therapies and for the sites and investigators engaged in those studies.

Each of us has probably faced a personal “defining professional moment,” when we had to utilize every skill in our arsenal and examine the motivations that led us to a career in oncology. However, it is clear from the forgoing clinical and research processes and guidelines that the COVID-19 pandemic is such a defining professional moment for each of us, in every community we serve.

Critical junctures like this cause more rapid behavior change and innovation than the slow-moving pace that characterizes our idealized preferences. As oncologists who embrace new data and behavioral change, we stand to learn processes that will facilitate more perfected systems of care than the one that preceded this unprecedented crisis, promote more efficient sharing of high-quality information, and improve the outcome for our future patients.


Dr. Lyss was an oncologist and researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

Two months after the first patient with COVID-19 was identified in China, the first case was reported in the United States in the Seattle, Washington, metropolitan area.

Seattle rapidly became the first US epicenter for COVID-19, and local experts are now offering their expertise and advice on how to provide optimal cancer care during the pandemic in a special feature published online March 20 in the Journal of the National Comprehensive Cancer Network.

“We began implementing measures in early March, including infection control and screening of visitors, staff, and patients at the door,” said lead author Masumi Ueda, MD, who holds positions at the Seattle Cancer Care Alliance, the University of Washington, and the Fred Hutchinson Research Center.

“A lot of changes have been implemented, and it changes on a daily basis. We are responding to the growing rate of COVID-19 infection in the community,” she told Medscape Medical News.

Ueda notes that as a result of the quick implementation of new procedures, so far, very few cancer patients at their facilities have been infected by the virus. “It has not hit our cancer population hard, which is a good thing,” she said.

Create “Incident Command Structure”

In sharing their experience, the authors emphasize the importance of keeping channels of communication open between all stakeholders ― administrators and staff, patients, caregivers, and the general public. They also recommend that each facility create an “incident command structure” that can provide early coordination of institution-wide efforts and that can rapidly respond to changing information.

Ueda noted that their command structure was set up very early on, “so we could get communication set up and start building an infrastructure for response.”

Several areas of care that required new strategies were addressed, both to protect patients and to work around staff shortages caused by possible exposure and/or school closings, as well as projected shortages of supplies and hospital resources.

First and foremost was to identify patients and visitors who had respiratory symptoms and to provide them with masks. Although this is always routine practice during the respiratory virus season, screening has now been initiated at entry points throughout the system.

“We were lucky in Seattle and Washington state in that the University of Washington virology lab developed PCR [polymerase chain reaction] testing early on for COVID-19, which subsequently got FDA approval,” said Ueda. “So we were able to have local testing and didn’t have to rely on the state lab. Testing has also been rapidly scaled up.”

Initiating a comprehensive policy for testing staff, tracking results and exposures for persons under investigation, and defining when it is possible to return to work are essential elements for maintaining a stable workforce. In addition, reinforcing a strict “stay at home when ill” policy and providing access to testing for symptomatic staff have been key to limiting exposures.

“What is unique to our region is that we had testing early on, and we are turning it around in 24 hours,” she pointed out. “This is important for staff to be able to return to work.” Currently, staff, patients, and visitors are being tested only if they show the cardinal symptoms associated with COVID-19: fever, shortness of breath, and cough, although muscle aches have recently been added to their testing protocol.

“I think if we had unlimited capacity, we might consider testing people who are asymptomatic,” Ueda noted, “although if you don’t have symptoms, you may not have the viral load needed for an accurate test.”

Educational materials explaining infection control were also needed for patients and families, along with signs and a website to provide COVID-19 education. These were quickly developed.

In addition, a telephone triage line was established for patients with mild symptoms in order to minimize exposures in clinics and to lessen the number of patients presenting at emergency departments.

Outpatient Care

Because theirs is a referral center, many cancer patients come from out of town, and so there is concern about exposing nonlocal patients to COVID-19 as the virus spreads in the Seattle area. In addition, staffing shortages due to factors such as illness, exposure, and school closures are anticipated.

To address these problems, an initial priority was to establish a “multilayer” coverage system for the clinics in the event that practitioners had to be quarantined on short notice, the authors explain.

One decision was to reschedule all wellness visits for current patients or to use telemedicine. Capacity for that option expanded quickly, which was greatly helped by the recent decision by the Centers for Medicare & Medicaid Services to lift Medicare restrictions on the use of certain telemedicine services.

Another approach is to defer all consultations for second opinions for patients who were already undergoing treatment and to increase clinic hours of operations and capabilities for acute evaluations. This helps reserve emergency departments and hospital resources for patients who require higher-level care, the authors comment.

Treatment Decisions

Treatment decisions were more challenging to make, the authors note. One decision was that, despite the risk for COVID-19 for patients with solid tumors, adjuvant therapy with curative intent should proceed, they note. Similarly, patients with metastatic disease might lose the window of opportunity for treatment if it is delayed.

Treatment for aggressive hematologic malignancies is usually urgent, and stem cell transplant and cellular immunotherapies that provide curative treatments cannot be delayed in many cases.

Enrollment in clinical trials will most likely be limited to those trials that are most likely to benefit the patient.

Ueda noted that, because their patients come from all over the country, they are now conducting consultations for stem cell transplant by telephone so that nonlocal patients do not have to travel to Seattle. “If there is some way we can delay the treatment, we have taken that approach,” Ueda told Medscape Medical News. “If we can divert a patient to an area that is not as heavily affected, that’s another option we are taking.”

Although cancer surgery is not considered elective, surgical intervention needs to be prioritized, the authors comment. In the Seattle system, there is currently a 2-week ban on elective surgery in the healthcare system, owing to limited availability of personal protective equipment (PPE), staffing, and beds.

The oncology teams are currently reviewing treatment regimens to determine which treatments might lessen immunosuppression and which treatment options can be moved from the inpatient to the outpatient setting or can be delayed.

Inpatient Care

For hospitalized patients, several issues are being addressed. The priority is to prepare for an upcoming shortage of beds and resources because of the surge of patients with COVID-19 that is predicted. For both clinic and hospitalized patients, shortages of blood products have necessitated stricter adherence to thresholds for transfusion, and consideration is being given to lowering those thresholds.

Another important problem is the need to conserve PPE, which includes masks, gowns, gloves, and other products. The Seattle teams have implemented solutions such as favoring handwashing with soap and water over the use of hand gel for standard-precaution rooms, limiting the number of personnel entering patient rooms (so as to use less PPE), and reducing nursing procedures that require PPE, such as measuring urine output, unless they are necessary.

In addition, a no-visitor policy has been adopted in inpatient units to conserve PPE, with the exception of end-of-life situations.

The Future

The future trajectory of the COVID-19 pandemic is uncertain, Ueda commented. She emphasized that “we must continue to prepare for its widespread impact. The unknown is what we are looking at. We are expecting it to evolve, and the number of infections cannot go down.”

Ueda and coauthors end their article on a positive note. “To many of us, this has become the health care challenge of our generation, one that modern cancer therapy has never had to face. We will prevail, and when the pandemic ends, we will all be proud of what we did for our patients and each other in this critical moment for humanity.”

Two months after the first patient with COVID-19 was identified in China, the first case was reported in the United States in the Seattle, Washington, metropolitan area.

Seattle rapidly became the first US epicenter for COVID-19, and local experts are now offering their expertise and advice on how to provide optimal cancer care during the pandemic in a special feature published online March 20 in the Journal of the National Comprehensive Cancer Network.

“We began implementing measures in early March, including infection control and screening of visitors, staff, and patients at the door,” said lead author Masumi Ueda, MD, who holds positions at the Seattle Cancer Care Alliance, the University of Washington, and the Fred Hutchinson Research Center.

“A lot of changes have been implemented, and it changes on a daily basis. We are responding to the growing rate of COVID-19 infection in the community,” she told Medscape Medical News.

Ueda notes that as a result of the quick implementation of new procedures, so far, very few cancer patients at their facilities have been infected by the virus. “It has not hit our cancer population hard, which is a good thing,” she said.

Create “Incident Command Structure”

In sharing their experience, the authors emphasize the importance of keeping channels of communication open between all stakeholders ― administrators and staff, patients, caregivers, and the general public. They also recommend that each facility create an “incident command structure” that can provide early coordination of institution-wide efforts and that can rapidly respond to changing information.

Ueda noted that their command structure was set up very early on, “so we could get communication set up and start building an infrastructure for response.”

Several areas of care that required new strategies were addressed, both to protect patients and to work around staff shortages caused by possible exposure and/or school closings, as well as projected shortages of supplies and hospital resources.

First and foremost was to identify patients and visitors who had respiratory symptoms and to provide them with masks. Although this is always routine practice during the respiratory virus season, screening has now been initiated at entry points throughout the system.

“We were lucky in Seattle and Washington state in that the University of Washington virology lab developed PCR [polymerase chain reaction] testing early on for COVID-19, which subsequently got FDA approval,” said Ueda. “So we were able to have local testing and didn’t have to rely on the state lab. Testing has also been rapidly scaled up.”

Initiating a comprehensive policy for testing staff, tracking results and exposures for persons under investigation, and defining when it is possible to return to work are essential elements for maintaining a stable workforce. In addition, reinforcing a strict “stay at home when ill” policy and providing access to testing for symptomatic staff have been key to limiting exposures.

“What is unique to our region is that we had testing early on, and we are turning it around in 24 hours,” she pointed out. “This is important for staff to be able to return to work.” Currently, staff, patients, and visitors are being tested only if they show the cardinal symptoms associated with COVID-19: fever, shortness of breath, and cough, although muscle aches have recently been added to their testing protocol.

“I think if we had unlimited capacity, we might consider testing people who are asymptomatic,” Ueda noted, “although if you don’t have symptoms, you may not have the viral load needed for an accurate test.”

Educational materials explaining infection control were also needed for patients and families, along with signs and a website to provide COVID-19 education. These were quickly developed.

In addition, a telephone triage line was established for patients with mild symptoms in order to minimize exposures in clinics and to lessen the number of patients presenting at emergency departments.

Outpatient Care

Because theirs is a referral center, many cancer patients come from out of town, and so there is concern about exposing nonlocal patients to COVID-19 as the virus spreads in the Seattle area. In addition, staffing shortages due to factors such as illness, exposure, and school closures are anticipated.

To address these problems, an initial priority was to establish a “multilayer” coverage system for the clinics in the event that practitioners had to be quarantined on short notice, the authors explain.

One decision was to reschedule all wellness visits for current patients or to use telemedicine. Capacity for that option expanded quickly, which was greatly helped by the recent decision by the Centers for Medicare & Medicaid Services to lift Medicare restrictions on the use of certain telemedicine services.

Another approach is to defer all consultations for second opinions for patients who were already undergoing treatment and to increase clinic hours of operations and capabilities for acute evaluations. This helps reserve emergency departments and hospital resources for patients who require higher-level care, the authors comment.

Treatment Decisions

Treatment decisions were more challenging to make, the authors note. One decision was that, despite the risk for COVID-19 for patients with solid tumors, adjuvant therapy with curative intent should proceed, they note. Similarly, patients with metastatic disease might lose the window of opportunity for treatment if it is delayed.

Treatment for aggressive hematologic malignancies is usually urgent, and stem cell transplant and cellular immunotherapies that provide curative treatments cannot be delayed in many cases.

Enrollment in clinical trials will most likely be limited to those trials that are most likely to benefit the patient.

Ueda noted that, because their patients come from all over the country, they are now conducting consultations for stem cell transplant by telephone so that nonlocal patients do not have to travel to Seattle. “If there is some way we can delay the treatment, we have taken that approach,” Ueda told Medscape Medical News. “If we can divert a patient to an area that is not as heavily affected, that’s another option we are taking.”

Although cancer surgery is not considered elective, surgical intervention needs to be prioritized, the authors comment. In the Seattle system, there is currently a 2-week ban on elective surgery in the healthcare system, owing to limited availability of personal protective equipment (PPE), staffing, and beds.

The oncology teams are currently reviewing treatment regimens to determine which treatments might lessen immunosuppression and which treatment options can be moved from the inpatient to the outpatient setting or can be delayed.

Inpatient Care

For hospitalized patients, several issues are being addressed. The priority is to prepare for an upcoming shortage of beds and resources because of the surge of patients with COVID-19 that is predicted. For both clinic and hospitalized patients, shortages of blood products have necessitated stricter adherence to thresholds for transfusion, and consideration is being given to lowering those thresholds.

Another important problem is the need to conserve PPE, which includes masks, gowns, gloves, and other products. The Seattle teams have implemented solutions such as favoring handwashing with soap and water over the use of hand gel for standard-precaution rooms, limiting the number of personnel entering patient rooms (so as to use less PPE), and reducing nursing procedures that require PPE, such as measuring urine output, unless they are necessary.

In addition, a no-visitor policy has been adopted in inpatient units to conserve PPE, with the exception of end-of-life situations.

The Future

The future trajectory of the COVID-19 pandemic is uncertain, Ueda commented. She emphasized that “we must continue to prepare for its widespread impact. The unknown is what we are looking at. We are expecting it to evolve, and the number of infections cannot go down.”

Ueda and coauthors end their article on a positive note. “To many of us, this has become the health care challenge of our generation, one that modern cancer therapy has never had to face. We will prevail, and when the pandemic ends, we will all be proud of what we did for our patients and each other in this critical moment for humanity.”

Two months after the first patient with COVID-19 was identified in China, the first case was reported in the United States in the Seattle, Washington, metropolitan area.

Seattle rapidly became the first US epicenter for COVID-19, and local experts are now offering their expertise and advice on how to provide optimal cancer care during the pandemic in a special feature published online March 20 in the Journal of the National Comprehensive Cancer Network.

“We began implementing measures in early March, including infection control and screening of visitors, staff, and patients at the door,” said lead author Masumi Ueda, MD, who holds positions at the Seattle Cancer Care Alliance, the University of Washington, and the Fred Hutchinson Research Center.

“A lot of changes have been implemented, and it changes on a daily basis. We are responding to the growing rate of COVID-19 infection in the community,” she told Medscape Medical News.

Ueda notes that as a result of the quick implementation of new procedures, so far, very few cancer patients at their facilities have been infected by the virus. “It has not hit our cancer population hard, which is a good thing,” she said.

Create “Incident Command Structure”

In sharing their experience, the authors emphasize the importance of keeping channels of communication open between all stakeholders ― administrators and staff, patients, caregivers, and the general public. They also recommend that each facility create an “incident command structure” that can provide early coordination of institution-wide efforts and that can rapidly respond to changing information.

Ueda noted that their command structure was set up very early on, “so we could get communication set up and start building an infrastructure for response.”

Several areas of care that required new strategies were addressed, both to protect patients and to work around staff shortages caused by possible exposure and/or school closings, as well as projected shortages of supplies and hospital resources.

First and foremost was to identify patients and visitors who had respiratory symptoms and to provide them with masks. Although this is always routine practice during the respiratory virus season, screening has now been initiated at entry points throughout the system.

“We were lucky in Seattle and Washington state in that the University of Washington virology lab developed PCR [polymerase chain reaction] testing early on for COVID-19, which subsequently got FDA approval,” said Ueda. “So we were able to have local testing and didn’t have to rely on the state lab. Testing has also been rapidly scaled up.”

Initiating a comprehensive policy for testing staff, tracking results and exposures for persons under investigation, and defining when it is possible to return to work are essential elements for maintaining a stable workforce. In addition, reinforcing a strict “stay at home when ill” policy and providing access to testing for symptomatic staff have been key to limiting exposures.

“What is unique to our region is that we had testing early on, and we are turning it around in 24 hours,” she pointed out. “This is important for staff to be able to return to work.” Currently, staff, patients, and visitors are being tested only if they show the cardinal symptoms associated with COVID-19: fever, shortness of breath, and cough, although muscle aches have recently been added to their testing protocol.

“I think if we had unlimited capacity, we might consider testing people who are asymptomatic,” Ueda noted, “although if you don’t have symptoms, you may not have the viral load needed for an accurate test.”

Educational materials explaining infection control were also needed for patients and families, along with signs and a website to provide COVID-19 education. These were quickly developed.

In addition, a telephone triage line was established for patients with mild symptoms in order to minimize exposures in clinics and to lessen the number of patients presenting at emergency departments.

Outpatient Care

Because theirs is a referral center, many cancer patients come from out of town, and so there is concern about exposing nonlocal patients to COVID-19 as the virus spreads in the Seattle area. In addition, staffing shortages due to factors such as illness, exposure, and school closures are anticipated.

To address these problems, an initial priority was to establish a “multilayer” coverage system for the clinics in the event that practitioners had to be quarantined on short notice, the authors explain.

One decision was to reschedule all wellness visits for current patients or to use telemedicine. Capacity for that option expanded quickly, which was greatly helped by the recent decision by the Centers for Medicare & Medicaid Services to lift Medicare restrictions on the use of certain telemedicine services.

Another approach is to defer all consultations for second opinions for patients who were already undergoing treatment and to increase clinic hours of operations and capabilities for acute evaluations. This helps reserve emergency departments and hospital resources for patients who require higher-level care, the authors comment.

Treatment Decisions

Treatment decisions were more challenging to make, the authors note. One decision was that, despite the risk for COVID-19 for patients with solid tumors, adjuvant therapy with curative intent should proceed, they note. Similarly, patients with metastatic disease might lose the window of opportunity for treatment if it is delayed.

Treatment for aggressive hematologic malignancies is usually urgent, and stem cell transplant and cellular immunotherapies that provide curative treatments cannot be delayed in many cases.

Enrollment in clinical trials will most likely be limited to those trials that are most likely to benefit the patient.

Ueda noted that, because their patients come from all over the country, they are now conducting consultations for stem cell transplant by telephone so that nonlocal patients do not have to travel to Seattle. “If there is some way we can delay the treatment, we have taken that approach,” Ueda told Medscape Medical News. “If we can divert a patient to an area that is not as heavily affected, that’s another option we are taking.”

Although cancer surgery is not considered elective, surgical intervention needs to be prioritized, the authors comment. In the Seattle system, there is currently a 2-week ban on elective surgery in the healthcare system, owing to limited availability of personal protective equipment (PPE), staffing, and beds.

The oncology teams are currently reviewing treatment regimens to determine which treatments might lessen immunosuppression and which treatment options can be moved from the inpatient to the outpatient setting or can be delayed.

Inpatient Care

For hospitalized patients, several issues are being addressed. The priority is to prepare for an upcoming shortage of beds and resources because of the surge of patients with COVID-19 that is predicted. For both clinic and hospitalized patients, shortages of blood products have necessitated stricter adherence to thresholds for transfusion, and consideration is being given to lowering those thresholds.

Another important problem is the need to conserve PPE, which includes masks, gowns, gloves, and other products. The Seattle teams have implemented solutions such as favoring handwashing with soap and water over the use of hand gel for standard-precaution rooms, limiting the number of personnel entering patient rooms (so as to use less PPE), and reducing nursing procedures that require PPE, such as measuring urine output, unless they are necessary.

In addition, a no-visitor policy has been adopted in inpatient units to conserve PPE, with the exception of end-of-life situations.

The Future

The future trajectory of the COVID-19 pandemic is uncertain, Ueda commented. She emphasized that “we must continue to prepare for its widespread impact. The unknown is what we are looking at. We are expecting it to evolve, and the number of infections cannot go down.”

Ueda and coauthors end their article on a positive note. “To many of us, this has become the health care challenge of our generation, one that modern cancer therapy has never had to face. We will prevail, and when the pandemic ends, we will all be proud of what we did for our patients and each other in this critical moment for humanity.”

As the coronavirus pandemic escalates in the United States, Medscape Oncology reached out to a group of our contributors and asked them to provide their perspective on how their oncology departments and centers are preparing. Here are their responses to a number of issues facing oncologists in the US and around the world.
 

Have you shifted nonurgent follow-up visits to telemedicine, either via video or phone?

Kathy Miller, MD, Associate Director of Indiana University Simon Cancer Center: We are reviewing our clinic schedules and identifying “routine” follow-up patients who can be rescheduled. When patients are contacted to reschedule, they are asked if they have any urgent, immediate concerns that need to be addressed before the new appointment. If yes, they are offered a virtual visit.

Don Dizon, MD, Director of Women’s Cancers, Lifespan Cancer Institute; Director of Medical Oncology, Rhode Island Hospital: We have started to do this in preparation for a surge of people with COVID-19. Patients who are in long-term follow-up (no evidence of disease at 3 years or longer, being seen annually) or those in routine surveillance after curative treatment (that is, seen every 3 months) as well as those being seen for supportive care–type visits, like sexual health or survivorship, are all being contacted and visits are being moved to telehealth.

Jeffrey S. Weber, MD, PhD, Deputy Director of the Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center: Yes. Any follow-up, nontreatment visits are done by phone or video if the patient agrees. (They all have).
 

Have you delayed or canceled cancer surgeries?

Ravi B. Parikh, MD, MPP, Medical oncologist at the University of Pennsylvania and the Philadelphia VA Medical Center: The University of Pennsylvania has taken this seriously. We’ve canceled all elective surgeries, have ramped up our telemedicine (video and phone) capabilities significantly, are limiting our appointments mostly to on-treatment visits, and have been asked to reconsider regular scans and reviews.

Dizon: We have not done this. There are apparently differences in interpretation in what institutions might mean as “elective surgeries.” At our institution, surgery for invasive malignancies is not elective. However, this may (or will) change if resources become an issue.

Lidia Schapira, MD, Associate Professor of Medicine and Director of Cancer Survivorship at the Stanford Comprehensive Cancer Institute: Delaying elective surgery is something that hospitals here have already implemented, and I imagine that this trend will spread. But it may be difficult to decide in situations that are not exactly “life-saving” but where an earlier intervention could preserve function or improve quality of life.

Mark A. Lewis, MD, Director of Gastrointestinal Oncology at Intermountain Healthcare in Utah: Cancer surgeries have not been deemed elective or delayed.

Have you delayed or altered the delivery of potentially immune-comprising treatments?

David Kerr, MD, Professor of Cancer Medicine at the University of Oxford in England: We are considering delaying initiation of our adjuvant colorectal cancer treatments, as we have data from our own QUASAR trials suggesting that patients who commence chemotherapy between 2 and 6 weeks do equally as well as those who begin 6-12 weeks after surgery.

Parikh: I personally haven’t delayed giving chemotherapy to avoid immune compromise, but I believe some others may have. It’s a delicate balance between wanting to ensure cancer control and making sure we are flattening the curve. As an example, though, I delayed three on-treatment visits for my clinic last Monday, and I converted 70% of my visits to telemedicine. However, I’m a genitourinary cancer specialist and the treatments I give are very different from others.

Lewis: The most difficult calculus is around adjuvant therapy. For metastatic patients, I am trying to use the least immunosuppressive regimen possible that will still control their disease. As you can imagine, it’s an assessment of competing risks.

Schapira: Patients who need essential anticancer therapy should still get it, but attempts to deintensify therapy should continue—for example, holding or postponing treatment without harm (based on evidence, not opinion). This may be possible for patients considering hormonal therapies for breast or prostate cancer.

Patients who need radiation should discuss the timing with their radiation oncologist. In some cases, it may be possible to delay treatment without affecting outcomes, but these decisions should be made carefully. Alternatively, shorter courses of radiation may be appropriate.
 

Have you advised your own patients differently given the high risk to cancer patients?

Kerr: We have factored potential infection with the virus into discussions where the benefits of chemotherapy are very marginal. This could tip the balance toward the patient deciding not to pursue chemotherapy.

Dizon: The data from China are not entirely crystal-clear. While they noted that people with active cancer and those who had a history of cancer are at increased risk for more severe infections and worse outcomes, the Chinese cohort was small, and compared with people without cancer, it tended to be much older and to be smokers (former or current). Having said this, we are counseling everyone about the importance of social distancing, washing hands, and not touching your face.

Lewis: If I have a complete blood count with a differential that includes lymphocytes, I can advise my lymphopenic patients (who are particularly vulnerable to viral infection) to take special precautions regarding social distancing in their own families.
 

Have any of your hospitalized patients been affected by policy changes to prepare beds/departments for the expected increase in COVID-19–positive patients?

Weber: Not yet.

Dizon: No, not at the moment.
 

Have you been asked to assist with other services or COVID-19 task forces?

Dizon: I am keenly involved in the preparations and modifications to procedures, including staffing decisions in outpatient, movement to telehealth, and work-from-home policies.

Lewis: I am engaged in system-wide COVID-19 efforts around oncology.

Kerr: Perhaps oddest of all, I am learning with some of our junior doctors to care for ventilated patients. I still consider myself enough of a general physician that I would hope to be able to contribute to the truly sick, but I accept that I do need an appropriate refresher course.

Bishal Gyawali, MD, PhD, medical oncologist at Queen’s University Cancer Research Institute: Queen’s Hospital medical students are now volunteering to help with daycare, groceries, and other tasks for staff who are working in the hospital.
 

Are you experiencing any shortages in personal protective equipment (PPE) at your center?

Miller: Some supplies are running short, though none are frankly out at this point. However, rationing and controls are in place to stretch the supplies as far as possible, including reusing some PPE.

Dizon: We are rationing face masks and N95 respirators, eye shields, and even surgical scrubs. We are talking about postponing elective surgery to save PPE but are not yet to that point. We’re asking that face masks be reused for at least 2 days, maybe longer. PPEs are one per day. Scrubs are kept secure.

Lewis: We are being very careful not to overuse PPE but currently have an adequate inventory. We have had to move gloves and masks to areas where they are not accessible to the general public, as otherwise they were being stolen (this started weeks ago).

Kerr: Our National Health System has an adequate supply of PPE equipment centrally, but there seems to be a problem with distribution, as some hospitals are reporting shortages.

Weber: Masks are in short supply, so they are being used for several days if not wet. We are short of plastic gowns and are using paper chemo gowns. Similar story at many places.

This article first appeared on Medscape.com.

As the coronavirus pandemic escalates in the United States, Medscape Oncology reached out to a group of our contributors and asked them to provide their perspective on how their oncology departments and centers are preparing. Here are their responses to a number of issues facing oncologists in the US and around the world.
 

Have you shifted nonurgent follow-up visits to telemedicine, either via video or phone?

Kathy Miller, MD, Associate Director of Indiana University Simon Cancer Center: We are reviewing our clinic schedules and identifying “routine” follow-up patients who can be rescheduled. When patients are contacted to reschedule, they are asked if they have any urgent, immediate concerns that need to be addressed before the new appointment. If yes, they are offered a virtual visit.

Don Dizon, MD, Director of Women’s Cancers, Lifespan Cancer Institute; Director of Medical Oncology, Rhode Island Hospital: We have started to do this in preparation for a surge of people with COVID-19. Patients who are in long-term follow-up (no evidence of disease at 3 years or longer, being seen annually) or those in routine surveillance after curative treatment (that is, seen every 3 months) as well as those being seen for supportive care–type visits, like sexual health or survivorship, are all being contacted and visits are being moved to telehealth.

Jeffrey S. Weber, MD, PhD, Deputy Director of the Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center: Yes. Any follow-up, nontreatment visits are done by phone or video if the patient agrees. (They all have).
 

Have you delayed or canceled cancer surgeries?

Ravi B. Parikh, MD, MPP, Medical oncologist at the University of Pennsylvania and the Philadelphia VA Medical Center: The University of Pennsylvania has taken this seriously. We’ve canceled all elective surgeries, have ramped up our telemedicine (video and phone) capabilities significantly, are limiting our appointments mostly to on-treatment visits, and have been asked to reconsider regular scans and reviews.

Dizon: We have not done this. There are apparently differences in interpretation in what institutions might mean as “elective surgeries.” At our institution, surgery for invasive malignancies is not elective. However, this may (or will) change if resources become an issue.

Lidia Schapira, MD, Associate Professor of Medicine and Director of Cancer Survivorship at the Stanford Comprehensive Cancer Institute: Delaying elective surgery is something that hospitals here have already implemented, and I imagine that this trend will spread. But it may be difficult to decide in situations that are not exactly “life-saving” but where an earlier intervention could preserve function or improve quality of life.

Mark A. Lewis, MD, Director of Gastrointestinal Oncology at Intermountain Healthcare in Utah: Cancer surgeries have not been deemed elective or delayed.

Have you delayed or altered the delivery of potentially immune-comprising treatments?

David Kerr, MD, Professor of Cancer Medicine at the University of Oxford in England: We are considering delaying initiation of our adjuvant colorectal cancer treatments, as we have data from our own QUASAR trials suggesting that patients who commence chemotherapy between 2 and 6 weeks do equally as well as those who begin 6-12 weeks after surgery.

Parikh: I personally haven’t delayed giving chemotherapy to avoid immune compromise, but I believe some others may have. It’s a delicate balance between wanting to ensure cancer control and making sure we are flattening the curve. As an example, though, I delayed three on-treatment visits for my clinic last Monday, and I converted 70% of my visits to telemedicine. However, I’m a genitourinary cancer specialist and the treatments I give are very different from others.

Lewis: The most difficult calculus is around adjuvant therapy. For metastatic patients, I am trying to use the least immunosuppressive regimen possible that will still control their disease. As you can imagine, it’s an assessment of competing risks.

Schapira: Patients who need essential anticancer therapy should still get it, but attempts to deintensify therapy should continue—for example, holding or postponing treatment without harm (based on evidence, not opinion). This may be possible for patients considering hormonal therapies for breast or prostate cancer.

Patients who need radiation should discuss the timing with their radiation oncologist. In some cases, it may be possible to delay treatment without affecting outcomes, but these decisions should be made carefully. Alternatively, shorter courses of radiation may be appropriate.
 

Have you advised your own patients differently given the high risk to cancer patients?

Kerr: We have factored potential infection with the virus into discussions where the benefits of chemotherapy are very marginal. This could tip the balance toward the patient deciding not to pursue chemotherapy.

Dizon: The data from China are not entirely crystal-clear. While they noted that people with active cancer and those who had a history of cancer are at increased risk for more severe infections and worse outcomes, the Chinese cohort was small, and compared with people without cancer, it tended to be much older and to be smokers (former or current). Having said this, we are counseling everyone about the importance of social distancing, washing hands, and not touching your face.

Lewis: If I have a complete blood count with a differential that includes lymphocytes, I can advise my lymphopenic patients (who are particularly vulnerable to viral infection) to take special precautions regarding social distancing in their own families.
 

Have any of your hospitalized patients been affected by policy changes to prepare beds/departments for the expected increase in COVID-19–positive patients?

Weber: Not yet.

Dizon: No, not at the moment.
 

Have you been asked to assist with other services or COVID-19 task forces?

Dizon: I am keenly involved in the preparations and modifications to procedures, including staffing decisions in outpatient, movement to telehealth, and work-from-home policies.

Lewis: I am engaged in system-wide COVID-19 efforts around oncology.

Kerr: Perhaps oddest of all, I am learning with some of our junior doctors to care for ventilated patients. I still consider myself enough of a general physician that I would hope to be able to contribute to the truly sick, but I accept that I do need an appropriate refresher course.

Bishal Gyawali, MD, PhD, medical oncologist at Queen’s University Cancer Research Institute: Queen’s Hospital medical students are now volunteering to help with daycare, groceries, and other tasks for staff who are working in the hospital.
 

Are you experiencing any shortages in personal protective equipment (PPE) at your center?

Miller: Some supplies are running short, though none are frankly out at this point. However, rationing and controls are in place to stretch the supplies as far as possible, including reusing some PPE.

Dizon: We are rationing face masks and N95 respirators, eye shields, and even surgical scrubs. We are talking about postponing elective surgery to save PPE but are not yet to that point. We’re asking that face masks be reused for at least 2 days, maybe longer. PPEs are one per day. Scrubs are kept secure.

Lewis: We are being very careful not to overuse PPE but currently have an adequate inventory. We have had to move gloves and masks to areas where they are not accessible to the general public, as otherwise they were being stolen (this started weeks ago).

Kerr: Our National Health System has an adequate supply of PPE equipment centrally, but there seems to be a problem with distribution, as some hospitals are reporting shortages.

Weber: Masks are in short supply, so they are being used for several days if not wet. We are short of plastic gowns and are using paper chemo gowns. Similar story at many places.

This article first appeared on Medscape.com.

As the coronavirus pandemic escalates in the United States, Medscape Oncology reached out to a group of our contributors and asked them to provide their perspective on how their oncology departments and centers are preparing. Here are their responses to a number of issues facing oncologists in the US and around the world.
 

Have you shifted nonurgent follow-up visits to telemedicine, either via video or phone?

Kathy Miller, MD, Associate Director of Indiana University Simon Cancer Center: We are reviewing our clinic schedules and identifying “routine” follow-up patients who can be rescheduled. When patients are contacted to reschedule, they are asked if they have any urgent, immediate concerns that need to be addressed before the new appointment. If yes, they are offered a virtual visit.

Don Dizon, MD, Director of Women’s Cancers, Lifespan Cancer Institute; Director of Medical Oncology, Rhode Island Hospital: We have started to do this in preparation for a surge of people with COVID-19. Patients who are in long-term follow-up (no evidence of disease at 3 years or longer, being seen annually) or those in routine surveillance after curative treatment (that is, seen every 3 months) as well as those being seen for supportive care–type visits, like sexual health or survivorship, are all being contacted and visits are being moved to telehealth.

Jeffrey S. Weber, MD, PhD, Deputy Director of the Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center: Yes. Any follow-up, nontreatment visits are done by phone or video if the patient agrees. (They all have).
 

Have you delayed or canceled cancer surgeries?

Ravi B. Parikh, MD, MPP, Medical oncologist at the University of Pennsylvania and the Philadelphia VA Medical Center: The University of Pennsylvania has taken this seriously. We’ve canceled all elective surgeries, have ramped up our telemedicine (video and phone) capabilities significantly, are limiting our appointments mostly to on-treatment visits, and have been asked to reconsider regular scans and reviews.

Dizon: We have not done this. There are apparently differences in interpretation in what institutions might mean as “elective surgeries.” At our institution, surgery for invasive malignancies is not elective. However, this may (or will) change if resources become an issue.

Lidia Schapira, MD, Associate Professor of Medicine and Director of Cancer Survivorship at the Stanford Comprehensive Cancer Institute: Delaying elective surgery is something that hospitals here have already implemented, and I imagine that this trend will spread. But it may be difficult to decide in situations that are not exactly “life-saving” but where an earlier intervention could preserve function or improve quality of life.

Mark A. Lewis, MD, Director of Gastrointestinal Oncology at Intermountain Healthcare in Utah: Cancer surgeries have not been deemed elective or delayed.

Have you delayed or altered the delivery of potentially immune-comprising treatments?

David Kerr, MD, Professor of Cancer Medicine at the University of Oxford in England: We are considering delaying initiation of our adjuvant colorectal cancer treatments, as we have data from our own QUASAR trials suggesting that patients who commence chemotherapy between 2 and 6 weeks do equally as well as those who begin 6-12 weeks after surgery.

Parikh: I personally haven’t delayed giving chemotherapy to avoid immune compromise, but I believe some others may have. It’s a delicate balance between wanting to ensure cancer control and making sure we are flattening the curve. As an example, though, I delayed three on-treatment visits for my clinic last Monday, and I converted 70% of my visits to telemedicine. However, I’m a genitourinary cancer specialist and the treatments I give are very different from others.

Lewis: The most difficult calculus is around adjuvant therapy. For metastatic patients, I am trying to use the least immunosuppressive regimen possible that will still control their disease. As you can imagine, it’s an assessment of competing risks.

Schapira: Patients who need essential anticancer therapy should still get it, but attempts to deintensify therapy should continue—for example, holding or postponing treatment without harm (based on evidence, not opinion). This may be possible for patients considering hormonal therapies for breast or prostate cancer.

Patients who need radiation should discuss the timing with their radiation oncologist. In some cases, it may be possible to delay treatment without affecting outcomes, but these decisions should be made carefully. Alternatively, shorter courses of radiation may be appropriate.
 

Have you advised your own patients differently given the high risk to cancer patients?

Kerr: We have factored potential infection with the virus into discussions where the benefits of chemotherapy are very marginal. This could tip the balance toward the patient deciding not to pursue chemotherapy.

Dizon: The data from China are not entirely crystal-clear. While they noted that people with active cancer and those who had a history of cancer are at increased risk for more severe infections and worse outcomes, the Chinese cohort was small, and compared with people without cancer, it tended to be much older and to be smokers (former or current). Having said this, we are counseling everyone about the importance of social distancing, washing hands, and not touching your face.

Lewis: If I have a complete blood count with a differential that includes lymphocytes, I can advise my lymphopenic patients (who are particularly vulnerable to viral infection) to take special precautions regarding social distancing in their own families.
 

Have any of your hospitalized patients been affected by policy changes to prepare beds/departments for the expected increase in COVID-19–positive patients?

Weber: Not yet.

Dizon: No, not at the moment.
 

Have you been asked to assist with other services or COVID-19 task forces?

Dizon: I am keenly involved in the preparations and modifications to procedures, including staffing decisions in outpatient, movement to telehealth, and work-from-home policies.

Lewis: I am engaged in system-wide COVID-19 efforts around oncology.

Kerr: Perhaps oddest of all, I am learning with some of our junior doctors to care for ventilated patients. I still consider myself enough of a general physician that I would hope to be able to contribute to the truly sick, but I accept that I do need an appropriate refresher course.

Bishal Gyawali, MD, PhD, medical oncologist at Queen’s University Cancer Research Institute: Queen’s Hospital medical students are now volunteering to help with daycare, groceries, and other tasks for staff who are working in the hospital.
 

Are you experiencing any shortages in personal protective equipment (PPE) at your center?

Miller: Some supplies are running short, though none are frankly out at this point. However, rationing and controls are in place to stretch the supplies as far as possible, including reusing some PPE.

Dizon: We are rationing face masks and N95 respirators, eye shields, and even surgical scrubs. We are talking about postponing elective surgery to save PPE but are not yet to that point. We’re asking that face masks be reused for at least 2 days, maybe longer. PPEs are one per day. Scrubs are kept secure.

Lewis: We are being very careful not to overuse PPE but currently have an adequate inventory. We have had to move gloves and masks to areas where they are not accessible to the general public, as otherwise they were being stolen (this started weeks ago).

Kerr: Our National Health System has an adequate supply of PPE equipment centrally, but there seems to be a problem with distribution, as some hospitals are reporting shortages.

Weber: Masks are in short supply, so they are being used for several days if not wet. We are short of plastic gowns and are using paper chemo gowns. Similar story at many places.

This article first appeared on Medscape.com.

Editor’s note: Find the latest COVID-19 news and guidance in Medscape’s Coronavirus Resource Center.
 

Even in the midst of the COVID-19 pandemic, cancer care must go on, but changes may need to be made in the way some care is delivered.

“We’re headed for a time when there will be significant disruptions in the care of patients with cancer,” said Len Lichtenfeld, MD, deputy chief medical officer of the American Cancer Society (ACS), in a statement. “For some it may be as straightforward as a delay in having elective surgery. For others it may be delaying preventive care or adjuvant chemotherapy that’s meant to keep cancer from returning or rescheduling appointments.”

Lichtenfeld emphasized that cancer care teams are going to do the best they can to deliver care to those most in need. However, even in those circumstances, it won’t be life as usual. “It will require patience on everyone’s part as we go through this pandemic,” he said.

“The way we treat cancer over the next few months will change enormously,” writes a British oncologist in an article published in the Guardian.

“As oncologists, we will have to find a tenuous balance between undertreating people with cancer, resulting in more deaths from the disease in the medium to long term, and increasing deaths from COVID-19 in a vulnerable patient population. Alongside our patients we will have to make difficult decisions regarding treatments, with only low-quality evidence to guide us,” writes Lucy Gossage, MD, consultant oncologist at Nottingham University Hospital, UK.

The evidence to date (from reports from China in Lancet Oncology) suggests that people with cancer have a significantly higher risk of severe illness resulting in intensive care admissions or death when infected with COVID-19, particularly if they recently had chemotherapy or surgery.

“Many of the oncology treatments we currently use, especially those given after surgery to reduce risk of cancer recurrence, have relatively small benefits,” she writes.

“In the current climate, the balance of offering these treatments may shift; a small reduction in risk of cancer recurrence over the next 5 years may be outweighed by the potential for a short-term increase in risk of death from COVID-19. In the long term, more people’s cancer will return if we aren’t able to offer these treatments,” she adds.

Postpone Routine Screening

One thing that can go on the back burner for now is routine cancer screening, which can be postponed for now in order to conserve health system resources and reduce contact with healthcare facilities, says the ACS.

“Patients seeking routine cancer screenings should delay those until further notice,” said Lichtenfeld. “While timely screening is important, the need to prevent the spread of coronavirus and to reduce the strain on the medical system is more important right now.”

But as soon as restrictions to slow the spread of COVID-19 are lifted and routine visits to health facilities are safe, regular screening tests should be rescheduled.

Guidance From ASCO

The American Society of Clinical Oncology (ASCO) has issued new guidance on caring for patients with cancer during the COVID-19 outbreak.

First and foremost, ASCO encourages providers, facilities, and anyone caring for patients with cancer to follow the existing guidelines from the Center for Disease Control and Prevention when possible.

ASCO highlights the CDC’s general recommendation for healthcare facilities that suggests “elective surgeries” at inpatient facilities be rescheduled if possible, which has also been recommended by the American College of Surgeons.

However, in many cases, cancer surgery is not elective but essential, it points out. So this is largely an individual determination that clinicians and patients will need to make, taking into account the potential harms of delaying needed cancer-related surgery.

Systemic treatments, including chemotherapy and immunotherapy, leave cancer patients vulnerable to infection, but ASCO says there is no direct evidence to support changes in regimens during the pandemic. Therefore, routinely stopping anticancer or immunosuppressive therapy is not recommended, as the balance of potential harms that may result from delaying or interrupting treatment versus the potential benefits of possibly preventing or delaying COVID-19 infection remains very unclear.

Clinical decisions must be individualized, ASCO emphasized, and suggested the following practice points be considered:

• For patients already in deep remission who are receiving maintenance therapy, stopping treatment may be an option.
• Some patients may be able to switch from IV to oral therapies, which would decrease the frequency of clinic visits.
• Decisions on modifying or withholding chemotherapy need to consider both the indication and goals of care, as well as where the patient is in the treatment regimen and tolerance to the therapy. As an example, the risk–benefit assessment for proceeding with chemotherapy in patients with untreated extensive small-cell lung cancer is quite different than proceeding with maintenance pemetrexed for metastatic non–small cell lung cancer.
• If local coronavirus transmission is an issue at a particular cancer center, reasonable options may include taking a 2-week treatment break or arranging treatment at a different facility.
• Evaluate if home infusion is medically and logistically feasible.
• In some settings, delaying or modifying adjuvant treatment presents a higher risk of compromised disease control and long-term survival than in others, but in cases where the absolute benefit of adjuvant chemotherapy may be quite small and other options are available, the risk of COVID-19 may be considered an additional factor when evaluating care.

Delay Stem Cell Transplants

For patients who are candidates for allogeneic stem cell transplantation, a delay may be reasonable if the patient is currently well controlled with conventional treatment, ASCO comments. It also directs clinicians to follow the recommendations provided by the American Society of Transplantation and Cellular Therapy and from the European Society for Blood and Marrow Transplantation regarding this issue.

Finally, there is also the question of prophylactic antiviral therapy: Should it be considered for cancer patients undergoing active therapy?

The answer to that question is currently unknown, says ASCO, but “this is an active area of research and evidence may be available at any time.”

This article first appeared on Medscape.com.

Editor’s note: Find the latest COVID-19 news and guidance in Medscape’s Coronavirus Resource Center.
 

Even in the midst of the COVID-19 pandemic, cancer care must go on, but changes may need to be made in the way some care is delivered.

“We’re headed for a time when there will be significant disruptions in the care of patients with cancer,” said Len Lichtenfeld, MD, deputy chief medical officer of the American Cancer Society (ACS), in a statement. “For some it may be as straightforward as a delay in having elective surgery. For others it may be delaying preventive care or adjuvant chemotherapy that’s meant to keep cancer from returning or rescheduling appointments.”

Lichtenfeld emphasized that cancer care teams are going to do the best they can to deliver care to those most in need. However, even in those circumstances, it won’t be life as usual. “It will require patience on everyone’s part as we go through this pandemic,” he said.

“The way we treat cancer over the next few months will change enormously,” writes a British oncologist in an article published in the Guardian.

“As oncologists, we will have to find a tenuous balance between undertreating people with cancer, resulting in more deaths from the disease in the medium to long term, and increasing deaths from COVID-19 in a vulnerable patient population. Alongside our patients we will have to make difficult decisions regarding treatments, with only low-quality evidence to guide us,” writes Lucy Gossage, MD, consultant oncologist at Nottingham University Hospital, UK.

The evidence to date (from reports from China in Lancet Oncology) suggests that people with cancer have a significantly higher risk of severe illness resulting in intensive care admissions or death when infected with COVID-19, particularly if they recently had chemotherapy or surgery.

“Many of the oncology treatments we currently use, especially those given after surgery to reduce risk of cancer recurrence, have relatively small benefits,” she writes.

“In the current climate, the balance of offering these treatments may shift; a small reduction in risk of cancer recurrence over the next 5 years may be outweighed by the potential for a short-term increase in risk of death from COVID-19. In the long term, more people’s cancer will return if we aren’t able to offer these treatments,” she adds.

Postpone Routine Screening

One thing that can go on the back burner for now is routine cancer screening, which can be postponed for now in order to conserve health system resources and reduce contact with healthcare facilities, says the ACS.

“Patients seeking routine cancer screenings should delay those until further notice,” said Lichtenfeld. “While timely screening is important, the need to prevent the spread of coronavirus and to reduce the strain on the medical system is more important right now.”

But as soon as restrictions to slow the spread of COVID-19 are lifted and routine visits to health facilities are safe, regular screening tests should be rescheduled.

Guidance From ASCO

The American Society of Clinical Oncology (ASCO) has issued new guidance on caring for patients with cancer during the COVID-19 outbreak.

First and foremost, ASCO encourages providers, facilities, and anyone caring for patients with cancer to follow the existing guidelines from the Center for Disease Control and Prevention when possible.

ASCO highlights the CDC’s general recommendation for healthcare facilities that suggests “elective surgeries” at inpatient facilities be rescheduled if possible, which has also been recommended by the American College of Surgeons.

However, in many cases, cancer surgery is not elective but essential, it points out. So this is largely an individual determination that clinicians and patients will need to make, taking into account the potential harms of delaying needed cancer-related surgery.

Systemic treatments, including chemotherapy and immunotherapy, leave cancer patients vulnerable to infection, but ASCO says there is no direct evidence to support changes in regimens during the pandemic. Therefore, routinely stopping anticancer or immunosuppressive therapy is not recommended, as the balance of potential harms that may result from delaying or interrupting treatment versus the potential benefits of possibly preventing or delaying COVID-19 infection remains very unclear.

Clinical decisions must be individualized, ASCO emphasized, and suggested the following practice points be considered:

• For patients already in deep remission who are receiving maintenance therapy, stopping treatment may be an option.
• Some patients may be able to switch from IV to oral therapies, which would decrease the frequency of clinic visits.
• Decisions on modifying or withholding chemotherapy need to consider both the indication and goals of care, as well as where the patient is in the treatment regimen and tolerance to the therapy. As an example, the risk–benefit assessment for proceeding with chemotherapy in patients with untreated extensive small-cell lung cancer is quite different than proceeding with maintenance pemetrexed for metastatic non–small cell lung cancer.
• If local coronavirus transmission is an issue at a particular cancer center, reasonable options may include taking a 2-week treatment break or arranging treatment at a different facility.
• Evaluate if home infusion is medically and logistically feasible.
• In some settings, delaying or modifying adjuvant treatment presents a higher risk of compromised disease control and long-term survival than in others, but in cases where the absolute benefit of adjuvant chemotherapy may be quite small and other options are available, the risk of COVID-19 may be considered an additional factor when evaluating care.

Delay Stem Cell Transplants

For patients who are candidates for allogeneic stem cell transplantation, a delay may be reasonable if the patient is currently well controlled with conventional treatment, ASCO comments. It also directs clinicians to follow the recommendations provided by the American Society of Transplantation and Cellular Therapy and from the European Society for Blood and Marrow Transplantation regarding this issue.

Finally, there is also the question of prophylactic antiviral therapy: Should it be considered for cancer patients undergoing active therapy?

The answer to that question is currently unknown, says ASCO, but “this is an active area of research and evidence may be available at any time.”

This article first appeared on Medscape.com.

Editor’s note: Find the latest COVID-19 news and guidance in Medscape’s Coronavirus Resource Center.
 

Even in the midst of the COVID-19 pandemic, cancer care must go on, but changes may need to be made in the way some care is delivered.

“We’re headed for a time when there will be significant disruptions in the care of patients with cancer,” said Len Lichtenfeld, MD, deputy chief medical officer of the American Cancer Society (ACS), in a statement. “For some it may be as straightforward as a delay in having elective surgery. For others it may be delaying preventive care or adjuvant chemotherapy that’s meant to keep cancer from returning or rescheduling appointments.”

Lichtenfeld emphasized that cancer care teams are going to do the best they can to deliver care to those most in need. However, even in those circumstances, it won’t be life as usual. “It will require patience on everyone’s part as we go through this pandemic,” he said.

“The way we treat cancer over the next few months will change enormously,” writes a British oncologist in an article published in the Guardian.

“As oncologists, we will have to find a tenuous balance between undertreating people with cancer, resulting in more deaths from the disease in the medium to long term, and increasing deaths from COVID-19 in a vulnerable patient population. Alongside our patients we will have to make difficult decisions regarding treatments, with only low-quality evidence to guide us,” writes Lucy Gossage, MD, consultant oncologist at Nottingham University Hospital, UK.

The evidence to date (from reports from China in Lancet Oncology) suggests that people with cancer have a significantly higher risk of severe illness resulting in intensive care admissions or death when infected with COVID-19, particularly if they recently had chemotherapy or surgery.

“Many of the oncology treatments we currently use, especially those given after surgery to reduce risk of cancer recurrence, have relatively small benefits,” she writes.

“In the current climate, the balance of offering these treatments may shift; a small reduction in risk of cancer recurrence over the next 5 years may be outweighed by the potential for a short-term increase in risk of death from COVID-19. In the long term, more people’s cancer will return if we aren’t able to offer these treatments,” she adds.

Postpone Routine Screening

One thing that can go on the back burner for now is routine cancer screening, which can be postponed for now in order to conserve health system resources and reduce contact with healthcare facilities, says the ACS.

“Patients seeking routine cancer screenings should delay those until further notice,” said Lichtenfeld. “While timely screening is important, the need to prevent the spread of coronavirus and to reduce the strain on the medical system is more important right now.”

But as soon as restrictions to slow the spread of COVID-19 are lifted and routine visits to health facilities are safe, regular screening tests should be rescheduled.

Guidance From ASCO

The American Society of Clinical Oncology (ASCO) has issued new guidance on caring for patients with cancer during the COVID-19 outbreak.

First and foremost, ASCO encourages providers, facilities, and anyone caring for patients with cancer to follow the existing guidelines from the Center for Disease Control and Prevention when possible.

ASCO highlights the CDC’s general recommendation for healthcare facilities that suggests “elective surgeries” at inpatient facilities be rescheduled if possible, which has also been recommended by the American College of Surgeons.

However, in many cases, cancer surgery is not elective but essential, it points out. So this is largely an individual determination that clinicians and patients will need to make, taking into account the potential harms of delaying needed cancer-related surgery.

Systemic treatments, including chemotherapy and immunotherapy, leave cancer patients vulnerable to infection, but ASCO says there is no direct evidence to support changes in regimens during the pandemic. Therefore, routinely stopping anticancer or immunosuppressive therapy is not recommended, as the balance of potential harms that may result from delaying or interrupting treatment versus the potential benefits of possibly preventing or delaying COVID-19 infection remains very unclear.

Clinical decisions must be individualized, ASCO emphasized, and suggested the following practice points be considered:

• For patients already in deep remission who are receiving maintenance therapy, stopping treatment may be an option.
• Some patients may be able to switch from IV to oral therapies, which would decrease the frequency of clinic visits.
• Decisions on modifying or withholding chemotherapy need to consider both the indication and goals of care, as well as where the patient is in the treatment regimen and tolerance to the therapy. As an example, the risk–benefit assessment for proceeding with chemotherapy in patients with untreated extensive small-cell lung cancer is quite different than proceeding with maintenance pemetrexed for metastatic non–small cell lung cancer.
• If local coronavirus transmission is an issue at a particular cancer center, reasonable options may include taking a 2-week treatment break or arranging treatment at a different facility.
• Evaluate if home infusion is medically and logistically feasible.
• In some settings, delaying or modifying adjuvant treatment presents a higher risk of compromised disease control and long-term survival than in others, but in cases where the absolute benefit of adjuvant chemotherapy may be quite small and other options are available, the risk of COVID-19 may be considered an additional factor when evaluating care.

Delay Stem Cell Transplants

For patients who are candidates for allogeneic stem cell transplantation, a delay may be reasonable if the patient is currently well controlled with conventional treatment, ASCO comments. It also directs clinicians to follow the recommendations provided by the American Society of Transplantation and Cellular Therapy and from the European Society for Blood and Marrow Transplantation regarding this issue.

Finally, there is also the question of prophylactic antiviral therapy: Should it be considered for cancer patients undergoing active therapy?

The answer to that question is currently unknown, says ASCO, but “this is an active area of research and evidence may be available at any time.”

This article first appeared on Medscape.com.

For patients age 75 and older with nonsquamous non–small cell lung cancer (NSCLC) not previously treated with chemotherapy, combination carboplatin and pemetrexed followed by pemetrexed maintenance is both effective and tolerable, suggest the results of a phase 3 trial.

The median overall survival was 18.7 months for patients randomized to carboplatin/pemetrexed and 15.5 months for patients randomized to docetaxel monotherapy.

The combination met the prespecified endpoint for noninferiority to docetaxel but was not shown to be superior in terms of overall survival, investigator Isamu Okamoto, MD, of Kyushu University in Fukuoka, Japan, and colleagues reported in JAMA Oncology.

Still, progression-free survival was significantly longer in the carboplatin/pemetrexed arm, and dose reductions were less frequent with the combination than with docetaxel.

“The combination of carboplatin and pemetrexed followed by pemetrexed maintenance ... provides a clinically significant benefit with regard to its effectiveness and tolerability,” the investigators wrote. “This combination should therefore be considered as a standard option for treatment in this setting.”

Dr. Okamoto and colleagues noted that the lung cancer incidence in elderly patients – 75 years and older – is increasing, and cytotoxic chemotherapy remains the standard treatment for patients whose tumors do not carry targetable mutations or are resistant to immunotherapy.

“In anticipation of a further increase in the number of elderly individuals with advanced NSCLC, it will be important to develop more optimal chemotherapeutic regimens for this patient group,” the investigators wrote.

To that end, they conducted a phase 3 trial of carboplatin/pemetrexed in patients aged 75 and older with NSCLC who had not been exposed to cytotoxic chemotherapy.
 

Patients and treatment

There were 433 patients enrolled in the trial. Their median age was 78 years (range, 75-88 years), and 57.7% were men. All patients had Eastern Cooperative Oncology Group performance status of 0 or 1.

Patients were stratified by clinical stage (III, IV, or recurrence), sex, epidermal growth factor receptor variant status (wild-type, exon 19 deletion, L858R variant of exon 21, or unknown), and treatment center.

The patients were then randomly assigned on a 1:1 basis to receive either intravenous docetaxel at 60 mg/m² for 60 minutes on day 1 every 3 weeks or pemetrexed at 500 mg/m² for 10 minutes followed by an infusion of carboplatin at an area under the curve of 5 for 30 minutes on day 1 every 3 weeks. The combination therapy was repeated for up to four courses and followed by 3-week courses of maintenance therapy with the same dose of pemetrexed.

Both regimens were continued until disease progression or the development of unacceptable toxicities.
 

Efficacy and safety

All 433 randomized patients were included in the efficacy analysis, but the safety analysis included 428 patients. Three patients assigned to docetaxel and two assigned to carboplatin/pemetrexed did not receive protocol treatment.

The respective median overall survival for the docetaxel and carboplatin/pemetrexed arms was 15.5 months and 18.7 months, which translated to a stratified hazard ratio for death of 0.85, meeting the prespecified noninferiority endpoint (P = .003).

However, the upper limit of the 95% confidence interval was 1.056, exceeding the prespecified superiority margin of 1.000. Therefore, the combination could not be proven superior to docetaxel with regard to overall survival.

On the other hand, progression-free survival was significantly longer with carboplatin/pemetrexed. The median progression-free survival was 6.4 months in the combination arm and 4.3 months in the docetaxel arm (unstratified HR, 0.739; P < .001).

The overall response rate with carboplatin/pemetrexed was 36.8%, compared with 28.2% for docetaxel, but this difference was not statistically significant.

Adverse events that were more common in the docetaxel arm than in the combination arm included grade 3/4 decreases in white blood cell count (68.7% and 28%, respectively), grade 3/4 decreases in neutrophil count (86% and 46.3%, respectively), and febrile neutropenia (17.8% and 4.2%, respectively).

Adverse events more frequently seen with the combination than with docetaxel included anemia (29.4% and 1.9%, respectively) and decreased platelet counts (25.7% and 1.4%, respectively).

Two patients in each arm died from treatment-related causes. In the docetaxel arm, the deaths were caused by acute respiratory distress syndrome and pneumonitis. In the combination arm, the deaths were caused by dyspnea and pneumonitis.

Approximately 29% of patients in each arm reported improvement in quality of life at 18 weeks, compared with baseline.

Performance status is key

A lung cancer specialist who was not involved in the study agreed with the authors that age should not be the primary determinant for choice of a treatment regimen.

“There’s a convergence of data over the last decade or so that has really clearly shown that our treatment decisions should be based on performance status much more than chronologic age, certainly for our patients who are in their 70s, and even potentially into their early 80s,” Howard (Jack) West, MD, of City of Hope Comprehensive Cancer Center in Duarte, Calif., said in an interview.

“The available data really say that patients with a good performance status who are in their 70s should be treated just like patients in their 60s and 50s,” he said.

He added, however, that for patients such as those in the study without targetable driver mutations, the best treatment would likely be immunotherapy or immunotherapy combined with chemotherapy.

“If there were a patient with a nonsquamous non–small cell lung cancer where we would be thinking about carboplatin and pemetrexed, I would go further than just carbo and pemetrexed; I would give carbo and pemetrexed with pembrolizumab for most of these patients,” he said.

Dr. West said the study primarily offers reassurances about the efficacy and tolerability of the carboplatin/pemetrexed combination in patients aged 75 years and older.

The study was funded by agencies of the Japanese government. The investigators disclosed relationships with Boehringer Ingelheim, AstraZeneca, Eli Lilly Japan KK, and many other companies. Dr. West disclosed consulting for Merck.

SOURCE: Okamoto I et al. JAMA Oncol. 2020 Mar 12. doi: 10.1001/jamaoncol.2019.6828.

For patients age 75 and older with nonsquamous non–small cell lung cancer (NSCLC) not previously treated with chemotherapy, combination carboplatin and pemetrexed followed by pemetrexed maintenance is both effective and tolerable, suggest the results of a phase 3 trial.

The median overall survival was 18.7 months for patients randomized to carboplatin/pemetrexed and 15.5 months for patients randomized to docetaxel monotherapy.

The combination met the prespecified endpoint for noninferiority to docetaxel but was not shown to be superior in terms of overall survival, investigator Isamu Okamoto, MD, of Kyushu University in Fukuoka, Japan, and colleagues reported in JAMA Oncology.

Still, progression-free survival was significantly longer in the carboplatin/pemetrexed arm, and dose reductions were less frequent with the combination than with docetaxel.

“The combination of carboplatin and pemetrexed followed by pemetrexed maintenance ... provides a clinically significant benefit with regard to its effectiveness and tolerability,” the investigators wrote. “This combination should therefore be considered as a standard option for treatment in this setting.”

Dr. Okamoto and colleagues noted that the lung cancer incidence in elderly patients – 75 years and older – is increasing, and cytotoxic chemotherapy remains the standard treatment for patients whose tumors do not carry targetable mutations or are resistant to immunotherapy.

“In anticipation of a further increase in the number of elderly individuals with advanced NSCLC, it will be important to develop more optimal chemotherapeutic regimens for this patient group,” the investigators wrote.

To that end, they conducted a phase 3 trial of carboplatin/pemetrexed in patients aged 75 and older with NSCLC who had not been exposed to cytotoxic chemotherapy.
 

Patients and treatment

There were 433 patients enrolled in the trial. Their median age was 78 years (range, 75-88 years), and 57.7% were men. All patients had Eastern Cooperative Oncology Group performance status of 0 or 1.

Patients were stratified by clinical stage (III, IV, or recurrence), sex, epidermal growth factor receptor variant status (wild-type, exon 19 deletion, L858R variant of exon 21, or unknown), and treatment center.

The patients were then randomly assigned on a 1:1 basis to receive either intravenous docetaxel at 60 mg/m² for 60 minutes on day 1 every 3 weeks or pemetrexed at 500 mg/m² for 10 minutes followed by an infusion of carboplatin at an area under the curve of 5 for 30 minutes on day 1 every 3 weeks. The combination therapy was repeated for up to four courses and followed by 3-week courses of maintenance therapy with the same dose of pemetrexed.

Both regimens were continued until disease progression or the development of unacceptable toxicities.
 

Efficacy and safety

All 433 randomized patients were included in the efficacy analysis, but the safety analysis included 428 patients. Three patients assigned to docetaxel and two assigned to carboplatin/pemetrexed did not receive protocol treatment.

The respective median overall survival for the docetaxel and carboplatin/pemetrexed arms was 15.5 months and 18.7 months, which translated to a stratified hazard ratio for death of 0.85, meeting the prespecified noninferiority endpoint (P = .003).

However, the upper limit of the 95% confidence interval was 1.056, exceeding the prespecified superiority margin of 1.000. Therefore, the combination could not be proven superior to docetaxel with regard to overall survival.

On the other hand, progression-free survival was significantly longer with carboplatin/pemetrexed. The median progression-free survival was 6.4 months in the combination arm and 4.3 months in the docetaxel arm (unstratified HR, 0.739; P < .001).

The overall response rate with carboplatin/pemetrexed was 36.8%, compared with 28.2% for docetaxel, but this difference was not statistically significant.

Adverse events that were more common in the docetaxel arm than in the combination arm included grade 3/4 decreases in white blood cell count (68.7% and 28%, respectively), grade 3/4 decreases in neutrophil count (86% and 46.3%, respectively), and febrile neutropenia (17.8% and 4.2%, respectively).

Adverse events more frequently seen with the combination than with docetaxel included anemia (29.4% and 1.9%, respectively) and decreased platelet counts (25.7% and 1.4%, respectively).

Two patients in each arm died from treatment-related causes. In the docetaxel arm, the deaths were caused by acute respiratory distress syndrome and pneumonitis. In the combination arm, the deaths were caused by dyspnea and pneumonitis.

Approximately 29% of patients in each arm reported improvement in quality of life at 18 weeks, compared with baseline.

Performance status is key

A lung cancer specialist who was not involved in the study agreed with the authors that age should not be the primary determinant for choice of a treatment regimen.

“There’s a convergence of data over the last decade or so that has really clearly shown that our treatment decisions should be based on performance status much more than chronologic age, certainly for our patients who are in their 70s, and even potentially into their early 80s,” Howard (Jack) West, MD, of City of Hope Comprehensive Cancer Center in Duarte, Calif., said in an interview.

“The available data really say that patients with a good performance status who are in their 70s should be treated just like patients in their 60s and 50s,” he said.

He added, however, that for patients such as those in the study without targetable driver mutations, the best treatment would likely be immunotherapy or immunotherapy combined with chemotherapy.

“If there were a patient with a nonsquamous non–small cell lung cancer where we would be thinking about carboplatin and pemetrexed, I would go further than just carbo and pemetrexed; I would give carbo and pemetrexed with pembrolizumab for most of these patients,” he said.

Dr. West said the study primarily offers reassurances about the efficacy and tolerability of the carboplatin/pemetrexed combination in patients aged 75 years and older.

The study was funded by agencies of the Japanese government. The investigators disclosed relationships with Boehringer Ingelheim, AstraZeneca, Eli Lilly Japan KK, and many other companies. Dr. West disclosed consulting for Merck.

SOURCE: Okamoto I et al. JAMA Oncol. 2020 Mar 12. doi: 10.1001/jamaoncol.2019.6828.

For patients age 75 and older with nonsquamous non–small cell lung cancer (NSCLC) not previously treated with chemotherapy, combination carboplatin and pemetrexed followed by pemetrexed maintenance is both effective and tolerable, suggest the results of a phase 3 trial.

The median overall survival was 18.7 months for patients randomized to carboplatin/pemetrexed and 15.5 months for patients randomized to docetaxel monotherapy.

The combination met the prespecified endpoint for noninferiority to docetaxel but was not shown to be superior in terms of overall survival, investigator Isamu Okamoto, MD, of Kyushu University in Fukuoka, Japan, and colleagues reported in JAMA Oncology.

Still, progression-free survival was significantly longer in the carboplatin/pemetrexed arm, and dose reductions were less frequent with the combination than with docetaxel.

“The combination of carboplatin and pemetrexed followed by pemetrexed maintenance ... provides a clinically significant benefit with regard to its effectiveness and tolerability,” the investigators wrote. “This combination should therefore be considered as a standard option for treatment in this setting.”

Dr. Okamoto and colleagues noted that the lung cancer incidence in elderly patients – 75 years and older – is increasing, and cytotoxic chemotherapy remains the standard treatment for patients whose tumors do not carry targetable mutations or are resistant to immunotherapy.

“In anticipation of a further increase in the number of elderly individuals with advanced NSCLC, it will be important to develop more optimal chemotherapeutic regimens for this patient group,” the investigators wrote.

To that end, they conducted a phase 3 trial of carboplatin/pemetrexed in patients aged 75 and older with NSCLC who had not been exposed to cytotoxic chemotherapy.
 

Patients and treatment

There were 433 patients enrolled in the trial. Their median age was 78 years (range, 75-88 years), and 57.7% were men. All patients had Eastern Cooperative Oncology Group performance status of 0 or 1.

Patients were stratified by clinical stage (III, IV, or recurrence), sex, epidermal growth factor receptor variant status (wild-type, exon 19 deletion, L858R variant of exon 21, or unknown), and treatment center.

The patients were then randomly assigned on a 1:1 basis to receive either intravenous docetaxel at 60 mg/m² for 60 minutes on day 1 every 3 weeks or pemetrexed at 500 mg/m² for 10 minutes followed by an infusion of carboplatin at an area under the curve of 5 for 30 minutes on day 1 every 3 weeks. The combination therapy was repeated for up to four courses and followed by 3-week courses of maintenance therapy with the same dose of pemetrexed.

Both regimens were continued until disease progression or the development of unacceptable toxicities.
 

Efficacy and safety

All 433 randomized patients were included in the efficacy analysis, but the safety analysis included 428 patients. Three patients assigned to docetaxel and two assigned to carboplatin/pemetrexed did not receive protocol treatment.

The respective median overall survival for the docetaxel and carboplatin/pemetrexed arms was 15.5 months and 18.7 months, which translated to a stratified hazard ratio for death of 0.85, meeting the prespecified noninferiority endpoint (P = .003).

However, the upper limit of the 95% confidence interval was 1.056, exceeding the prespecified superiority margin of 1.000. Therefore, the combination could not be proven superior to docetaxel with regard to overall survival.

On the other hand, progression-free survival was significantly longer with carboplatin/pemetrexed. The median progression-free survival was 6.4 months in the combination arm and 4.3 months in the docetaxel arm (unstratified HR, 0.739; P < .001).

The overall response rate with carboplatin/pemetrexed was 36.8%, compared with 28.2% for docetaxel, but this difference was not statistically significant.

Adverse events that were more common in the docetaxel arm than in the combination arm included grade 3/4 decreases in white blood cell count (68.7% and 28%, respectively), grade 3/4 decreases in neutrophil count (86% and 46.3%, respectively), and febrile neutropenia (17.8% and 4.2%, respectively).

Adverse events more frequently seen with the combination than with docetaxel included anemia (29.4% and 1.9%, respectively) and decreased platelet counts (25.7% and 1.4%, respectively).

Two patients in each arm died from treatment-related causes. In the docetaxel arm, the deaths were caused by acute respiratory distress syndrome and pneumonitis. In the combination arm, the deaths were caused by dyspnea and pneumonitis.

Approximately 29% of patients in each arm reported improvement in quality of life at 18 weeks, compared with baseline.

Performance status is key

A lung cancer specialist who was not involved in the study agreed with the authors that age should not be the primary determinant for choice of a treatment regimen.

“There’s a convergence of data over the last decade or so that has really clearly shown that our treatment decisions should be based on performance status much more than chronologic age, certainly for our patients who are in their 70s, and even potentially into their early 80s,” Howard (Jack) West, MD, of City of Hope Comprehensive Cancer Center in Duarte, Calif., said in an interview.

“The available data really say that patients with a good performance status who are in their 70s should be treated just like patients in their 60s and 50s,” he said.

He added, however, that for patients such as those in the study without targetable driver mutations, the best treatment would likely be immunotherapy or immunotherapy combined with chemotherapy.

“If there were a patient with a nonsquamous non–small cell lung cancer where we would be thinking about carboplatin and pemetrexed, I would go further than just carbo and pemetrexed; I would give carbo and pemetrexed with pembrolizumab for most of these patients,” he said.

Dr. West said the study primarily offers reassurances about the efficacy and tolerability of the carboplatin/pemetrexed combination in patients aged 75 years and older.

The study was funded by agencies of the Japanese government. The investigators disclosed relationships with Boehringer Ingelheim, AstraZeneca, Eli Lilly Japan KK, and many other companies. Dr. West disclosed consulting for Merck.

SOURCE: Okamoto I et al. JAMA Oncol. 2020 Mar 12. doi: 10.1001/jamaoncol.2019.6828.

Combination apatinib and vinorelbine “may have potential” for treating patients with wild-type, advanced non–small cell lung cancer (NSCLC) who failed at least two prior lines of chemotherapy, according to researchers.

In a phase 2 trial, apatinib plus vinorelbine produced an overall response rate of 36.7% and a disease control rate of 76.7%. Nearly half of patients required dose reductions, and 17% discontinued treatment due to adverse events.

Xiangyu Zhang, MD, of Hunan Cancer Hospital in Changsha, China, and colleagues conducted this trial (NCT03652857) and detailed the results in JAMA Network Open.

The researchers noted that there is no standard treatment strategy for patients who have advanced NSCLC without actionable mutations and have failed two or more lines of chemotherapy. So the team tested apatinib plus vinorelbine in 30 such patients.

The patients’ median age was 63 years (range, 34-78 years), 60% were men, and 90% had stage IV disease. They had received a median of 2 (range, 2-5) prior lines of chemotherapy.

In this study, patients received apatinib at 500 mg once daily and vinorelbine at 60 mg/m² once weekly. The dose of apatinib could be interrupted or reduced to manage adverse events. Patients could receive 250 mg or 500 mg on alternate days or 250 mg once daily. Patients were treated until they progressed, withdrew, or had unacceptable adverse events.
 

Results

Patients were treated for a median of 4 months (range, 1-22 months), and the median follow-up was 11 months (range, 4.5-14.1 months). Most patients (n = 25) continued treatment until they progressed, 17 were able to remain on the 500-mg dose of apatinib, 13 received the 250-mg dose of apatinib, and 5 patients discontinued treatment due to adverse events.

The overall response rate was 36.7%, and the disease control rate, defined as the proportion of patients with complete response, partial response, and stable disease, was 76.7%. There were no complete responses, 11 partial responses, 12 patients with stable disease, and 7 patients who progressed. Rates of response, disease control, and progression were similar whether patients received the 500-mg dose of apatinib or the 250-mg dose.

The median progression-free survival was 4.5 months, and the median overall survival was 10 months.

Hand-foot syndrome was the most common adverse event, with grade 1-2 hand-foot syndrome occurring in 13 patients (43%), grade 3 occurring in 5 patients (17%), and grade 4 occurring in 1 patient (3%).

The adverse events that led to treatment discontinuation were grade 3 weakness (n = 1), pleural effusion (n = 1), fungal infection (n = 1), and grade 3 hand-foot syndrome (n = 2). There were no fatal adverse events.

“[The] combination of apatinib and oral vinorelbine has promising efficacy and manageable toxic effects as a third-line or subsequent-line treatment in patients with driver variation-negative advanced NCSLC,” the researchers concluded. “Further evaluation of this combination in phase 3 trials is warranted.”

The current study was funded by grants from the National Natural Science Foundation of China and the Hunan Natural Science Foundation. The researchers disclosed no conflicts of interest.

jensmith@mdedge.com

SOURCE: Zhang X et al. JAMA Netw Open. 2020;3(3):e201226. doi: 10.1001/jamanetworkopen.2020.12.

Combination apatinib and vinorelbine “may have potential” for treating patients with wild-type, advanced non–small cell lung cancer (NSCLC) who failed at least two prior lines of chemotherapy, according to researchers.

In a phase 2 trial, apatinib plus vinorelbine produced an overall response rate of 36.7% and a disease control rate of 76.7%. Nearly half of patients required dose reductions, and 17% discontinued treatment due to adverse events.

Xiangyu Zhang, MD, of Hunan Cancer Hospital in Changsha, China, and colleagues conducted this trial (NCT03652857) and detailed the results in JAMA Network Open.

The researchers noted that there is no standard treatment strategy for patients who have advanced NSCLC without actionable mutations and have failed two or more lines of chemotherapy. So the team tested apatinib plus vinorelbine in 30 such patients.

The patients’ median age was 63 years (range, 34-78 years), 60% were men, and 90% had stage IV disease. They had received a median of 2 (range, 2-5) prior lines of chemotherapy.

In this study, patients received apatinib at 500 mg once daily and vinorelbine at 60 mg/m² once weekly. The dose of apatinib could be interrupted or reduced to manage adverse events. Patients could receive 250 mg or 500 mg on alternate days or 250 mg once daily. Patients were treated until they progressed, withdrew, or had unacceptable adverse events.
 

Results

Patients were treated for a median of 4 months (range, 1-22 months), and the median follow-up was 11 months (range, 4.5-14.1 months). Most patients (n = 25) continued treatment until they progressed, 17 were able to remain on the 500-mg dose of apatinib, 13 received the 250-mg dose of apatinib, and 5 patients discontinued treatment due to adverse events.

The overall response rate was 36.7%, and the disease control rate, defined as the proportion of patients with complete response, partial response, and stable disease, was 76.7%. There were no complete responses, 11 partial responses, 12 patients with stable disease, and 7 patients who progressed. Rates of response, disease control, and progression were similar whether patients received the 500-mg dose of apatinib or the 250-mg dose.

The median progression-free survival was 4.5 months, and the median overall survival was 10 months.

Hand-foot syndrome was the most common adverse event, with grade 1-2 hand-foot syndrome occurring in 13 patients (43%), grade 3 occurring in 5 patients (17%), and grade 4 occurring in 1 patient (3%).

The adverse events that led to treatment discontinuation were grade 3 weakness (n = 1), pleural effusion (n = 1), fungal infection (n = 1), and grade 3 hand-foot syndrome (n = 2). There were no fatal adverse events.

“[The] combination of apatinib and oral vinorelbine has promising efficacy and manageable toxic effects as a third-line or subsequent-line treatment in patients with driver variation-negative advanced NCSLC,” the researchers concluded. “Further evaluation of this combination in phase 3 trials is warranted.”

The current study was funded by grants from the National Natural Science Foundation of China and the Hunan Natural Science Foundation. The researchers disclosed no conflicts of interest.

jensmith@mdedge.com

SOURCE: Zhang X et al. JAMA Netw Open. 2020;3(3):e201226. doi: 10.1001/jamanetworkopen.2020.12.

Combination apatinib and vinorelbine “may have potential” for treating patients with wild-type, advanced non–small cell lung cancer (NSCLC) who failed at least two prior lines of chemotherapy, according to researchers.

In a phase 2 trial, apatinib plus vinorelbine produced an overall response rate of 36.7% and a disease control rate of 76.7%. Nearly half of patients required dose reductions, and 17% discontinued treatment due to adverse events.

Xiangyu Zhang, MD, of Hunan Cancer Hospital in Changsha, China, and colleagues conducted this trial (NCT03652857) and detailed the results in JAMA Network Open.

The researchers noted that there is no standard treatment strategy for patients who have advanced NSCLC without actionable mutations and have failed two or more lines of chemotherapy. So the team tested apatinib plus vinorelbine in 30 such patients.

The patients’ median age was 63 years (range, 34-78 years), 60% were men, and 90% had stage IV disease. They had received a median of 2 (range, 2-5) prior lines of chemotherapy.

In this study, patients received apatinib at 500 mg once daily and vinorelbine at 60 mg/m² once weekly. The dose of apatinib could be interrupted or reduced to manage adverse events. Patients could receive 250 mg or 500 mg on alternate days or 250 mg once daily. Patients were treated until they progressed, withdrew, or had unacceptable adverse events.
 

Results

Patients were treated for a median of 4 months (range, 1-22 months), and the median follow-up was 11 months (range, 4.5-14.1 months). Most patients (n = 25) continued treatment until they progressed, 17 were able to remain on the 500-mg dose of apatinib, 13 received the 250-mg dose of apatinib, and 5 patients discontinued treatment due to adverse events.

The overall response rate was 36.7%, and the disease control rate, defined as the proportion of patients with complete response, partial response, and stable disease, was 76.7%. There were no complete responses, 11 partial responses, 12 patients with stable disease, and 7 patients who progressed. Rates of response, disease control, and progression were similar whether patients received the 500-mg dose of apatinib or the 250-mg dose.

The median progression-free survival was 4.5 months, and the median overall survival was 10 months.

Hand-foot syndrome was the most common adverse event, with grade 1-2 hand-foot syndrome occurring in 13 patients (43%), grade 3 occurring in 5 patients (17%), and grade 4 occurring in 1 patient (3%).

The adverse events that led to treatment discontinuation were grade 3 weakness (n = 1), pleural effusion (n = 1), fungal infection (n = 1), and grade 3 hand-foot syndrome (n = 2). There were no fatal adverse events.

“[The] combination of apatinib and oral vinorelbine has promising efficacy and manageable toxic effects as a third-line or subsequent-line treatment in patients with driver variation-negative advanced NCSLC,” the researchers concluded. “Further evaluation of this combination in phase 3 trials is warranted.”

The current study was funded by grants from the National Natural Science Foundation of China and the Hunan Natural Science Foundation. The researchers disclosed no conflicts of interest.

jensmith@mdedge.com

SOURCE: Zhang X et al. JAMA Netw Open. 2020;3(3):e201226. doi: 10.1001/jamanetworkopen.2020.12.