Jennifer Smith

Cancer type, stage, and recent treatment may affect outcomes of COVID-19 in cancer patients, according to a study of patients from China.

The data showed that patients with hematologic malignancies and those with metastatic cancers had higher risks of developing severe or critical COVID-19 symptoms, being admitted to the ICU, requiring ventilation, and dying.

On the other hand, patients with nonmetastatic cancer had outcomes comparable to those of noncancer patients with COVID-19.

Similarly, cancer patients who had recently undergone surgery or received immunotherapy were more likely to have poor outcomes, whereas cancer patients treated with radiotherapy had outcomes similar to those of noncancer COVID-19 patients.

Hongbing Cai, MD, of Zhongnan Hospital of Wuhan University in China, presented these results at the AACR virtual meeting I. The results also were published in Cancer Discovery.
 

Cancer vs. noncancer patients

The study included 105 cancer patients with COVID-19 who were treated from Jan. 1 to Feb. 24, 2020, at 14 hospitals in Wuhan, China. Patients had lung (20.95%), gastrointestinal (12.38%), breast (10.48%), and thyroid cancers (10.48%) as well as hematologic malignancies (8.57%). Dr. Cai and colleagues matched the COVID-19 cancer patients to 536 COVID-19 patients without cancer. Patients were matched by hospital, duration of hospitalization, and age.

“COVID-19 patients with cancer had higher risks of all severe outcomes,” Dr. Cai noted.

Compared with noncancer patients, the cancer patients had a higher risk of:

• Severe or critical COVID-19 symptoms – odds ratio, 2.79 (P < .01).
• Being admitted to the ICU – OR, 2.84 (P < .01).
• Requiring invasive mechanical ventilation – OR, 14 (P < .01).
• Death – OR, 2.34 (P = .03).

Cancer type and stage

Dr. Cai noted that outcomes were the worst among patients with hematologic malignancies and those with metastatic cancer (stage IV).

Compared with patients without cancer, those with hematologic malignancies had a higher risk of:

• Severe/critical symptoms – OR, 10.61 (P < .01).
• ICU admission – OR, 9.66 (P < .01).
• Invasive mechanical ventilation – OR, 38 (P < .01).
• Death – OR, 9.07 (P = .01).

Compared with patients without cancer, those with metastatic cancer had a higher risk of:

• Severe/critical symptoms – OR, 5.97 (P < .01).
• ICU admission – OR, 6.59 (P < 0.01).
• Invasive mechanical ventilation – OR, 55.42 (P < .01).
• Death – OR, 5.58 (P = .01).

On the other hand, outcomes in patients with nonmetastatic cancer were not significantly different from outcomes in patients without cancer (P > .05 for all outcomes).
 

Cancer treatment

The treatments cancer patients received within 40 days before the onset of COVID-19 symptoms were radiotherapy (12.26%), chemotherapy (14.15%), surgery (7.62%), targeted therapies (3.81%), and immunotherapy (5.71%).

Compared with patients without cancer, those who received immunotherapy had a higher risk of:

• Severe/critical symptoms – OR, 10.61 (P < .01).
• Death – OR, 9.07 (P = .04).

Patients who underwent surgery had a higher risk of:

• Severe/critical symptoms – OR, 8.84 (P < .01).
• ICU admission – OR, 7.24 (P = .02).
• Invasive mechanical ventilation – OR, 44.33 (P < .01).

Conversely, outcomes in cancer patients who received radiotherapy were not significantly different from outcomes in patients without cancer (P > .10 for all).

These results suggest that “postponing surgery should be considered in outbreak areas,” Dr. Cai said, adding that scheduled radiotherapy can go ahead but with “intensive protection and surveillance.”

Dr. Cai said it remains to be seen whether patients with early-stage cancer need to postpone their treatments during the COVID-19 pandemic or whether immunotherapy aggravates severe outcomes in cancer patients with COVID-19. For now, she said, cancer patients should have individualized treatment plans based on their tumor type and stage.

Dr. Cai disclosed no conflicts of interest. This study was supported by the National Natural Science Foundation of China, the Singapore Ministry of Health’s National Medical Research Council, the National Institutes of Health/National Heart, Lung, and Blood Institute, and the Xiu Research Fund.

jensmith@mdedge.com

SOURCE: Cai H. AACR 2020. Patients with cancer appear more vulnerable to SARS-COV-2: A multicenter study during the COVID-19 outbreak; Dai M et al. Cancer Discov. 2020 Apr 28. doi: 10.1158/2159-8290.CD-20-0422.

Cancer type, stage, and recent treatment may affect outcomes of COVID-19 in cancer patients, according to a study of patients from China.

The data showed that patients with hematologic malignancies and those with metastatic cancers had higher risks of developing severe or critical COVID-19 symptoms, being admitted to the ICU, requiring ventilation, and dying.

On the other hand, patients with nonmetastatic cancer had outcomes comparable to those of noncancer patients with COVID-19.

Similarly, cancer patients who had recently undergone surgery or received immunotherapy were more likely to have poor outcomes, whereas cancer patients treated with radiotherapy had outcomes similar to those of noncancer COVID-19 patients.

Hongbing Cai, MD, of Zhongnan Hospital of Wuhan University in China, presented these results at the AACR virtual meeting I. The results also were published in Cancer Discovery.
 

Cancer vs. noncancer patients

The study included 105 cancer patients with COVID-19 who were treated from Jan. 1 to Feb. 24, 2020, at 14 hospitals in Wuhan, China. Patients had lung (20.95%), gastrointestinal (12.38%), breast (10.48%), and thyroid cancers (10.48%) as well as hematologic malignancies (8.57%). Dr. Cai and colleagues matched the COVID-19 cancer patients to 536 COVID-19 patients without cancer. Patients were matched by hospital, duration of hospitalization, and age.

“COVID-19 patients with cancer had higher risks of all severe outcomes,” Dr. Cai noted.

Compared with noncancer patients, the cancer patients had a higher risk of:

• Severe or critical COVID-19 symptoms – odds ratio, 2.79 (P < .01).
• Being admitted to the ICU – OR, 2.84 (P < .01).
• Requiring invasive mechanical ventilation – OR, 14 (P < .01).
• Death – OR, 2.34 (P = .03).

Cancer type and stage

Dr. Cai noted that outcomes were the worst among patients with hematologic malignancies and those with metastatic cancer (stage IV).

Compared with patients without cancer, those with hematologic malignancies had a higher risk of:

• Severe/critical symptoms – OR, 10.61 (P < .01).
• ICU admission – OR, 9.66 (P < .01).
• Invasive mechanical ventilation – OR, 38 (P < .01).
• Death – OR, 9.07 (P = .01).

Compared with patients without cancer, those with metastatic cancer had a higher risk of:

• Severe/critical symptoms – OR, 5.97 (P < .01).
• ICU admission – OR, 6.59 (P < 0.01).
• Invasive mechanical ventilation – OR, 55.42 (P < .01).
• Death – OR, 5.58 (P = .01).

On the other hand, outcomes in patients with nonmetastatic cancer were not significantly different from outcomes in patients without cancer (P > .05 for all outcomes).
 

Cancer treatment

The treatments cancer patients received within 40 days before the onset of COVID-19 symptoms were radiotherapy (12.26%), chemotherapy (14.15%), surgery (7.62%), targeted therapies (3.81%), and immunotherapy (5.71%).

Compared with patients without cancer, those who received immunotherapy had a higher risk of:

• Severe/critical symptoms – OR, 10.61 (P < .01).
• Death – OR, 9.07 (P = .04).

Patients who underwent surgery had a higher risk of:

• Severe/critical symptoms – OR, 8.84 (P < .01).
• ICU admission – OR, 7.24 (P = .02).
• Invasive mechanical ventilation – OR, 44.33 (P < .01).

Conversely, outcomes in cancer patients who received radiotherapy were not significantly different from outcomes in patients without cancer (P > .10 for all).

These results suggest that “postponing surgery should be considered in outbreak areas,” Dr. Cai said, adding that scheduled radiotherapy can go ahead but with “intensive protection and surveillance.”

Dr. Cai said it remains to be seen whether patients with early-stage cancer need to postpone their treatments during the COVID-19 pandemic or whether immunotherapy aggravates severe outcomes in cancer patients with COVID-19. For now, she said, cancer patients should have individualized treatment plans based on their tumor type and stage.

Dr. Cai disclosed no conflicts of interest. This study was supported by the National Natural Science Foundation of China, the Singapore Ministry of Health’s National Medical Research Council, the National Institutes of Health/National Heart, Lung, and Blood Institute, and the Xiu Research Fund.

jensmith@mdedge.com

SOURCE: Cai H. AACR 2020. Patients with cancer appear more vulnerable to SARS-COV-2: A multicenter study during the COVID-19 outbreak; Dai M et al. Cancer Discov. 2020 Apr 28. doi: 10.1158/2159-8290.CD-20-0422.

Cancer type, stage, and recent treatment may affect outcomes of COVID-19 in cancer patients, according to a study of patients from China.

The data showed that patients with hematologic malignancies and those with metastatic cancers had higher risks of developing severe or critical COVID-19 symptoms, being admitted to the ICU, requiring ventilation, and dying.

On the other hand, patients with nonmetastatic cancer had outcomes comparable to those of noncancer patients with COVID-19.

Similarly, cancer patients who had recently undergone surgery or received immunotherapy were more likely to have poor outcomes, whereas cancer patients treated with radiotherapy had outcomes similar to those of noncancer COVID-19 patients.

Hongbing Cai, MD, of Zhongnan Hospital of Wuhan University in China, presented these results at the AACR virtual meeting I. The results also were published in Cancer Discovery.
 

Cancer vs. noncancer patients

The study included 105 cancer patients with COVID-19 who were treated from Jan. 1 to Feb. 24, 2020, at 14 hospitals in Wuhan, China. Patients had lung (20.95%), gastrointestinal (12.38%), breast (10.48%), and thyroid cancers (10.48%) as well as hematologic malignancies (8.57%). Dr. Cai and colleagues matched the COVID-19 cancer patients to 536 COVID-19 patients without cancer. Patients were matched by hospital, duration of hospitalization, and age.

“COVID-19 patients with cancer had higher risks of all severe outcomes,” Dr. Cai noted.

Compared with noncancer patients, the cancer patients had a higher risk of:

• Severe or critical COVID-19 symptoms – odds ratio, 2.79 (P < .01).
• Being admitted to the ICU – OR, 2.84 (P < .01).
• Requiring invasive mechanical ventilation – OR, 14 (P < .01).
• Death – OR, 2.34 (P = .03).

Cancer type and stage

Dr. Cai noted that outcomes were the worst among patients with hematologic malignancies and those with metastatic cancer (stage IV).

Compared with patients without cancer, those with hematologic malignancies had a higher risk of:

• Severe/critical symptoms – OR, 10.61 (P < .01).
• ICU admission – OR, 9.66 (P < .01).
• Invasive mechanical ventilation – OR, 38 (P < .01).
• Death – OR, 9.07 (P = .01).

Compared with patients without cancer, those with metastatic cancer had a higher risk of:

• Severe/critical symptoms – OR, 5.97 (P < .01).
• ICU admission – OR, 6.59 (P < 0.01).
• Invasive mechanical ventilation – OR, 55.42 (P < .01).
• Death – OR, 5.58 (P = .01).

On the other hand, outcomes in patients with nonmetastatic cancer were not significantly different from outcomes in patients without cancer (P > .05 for all outcomes).
 

Cancer treatment

The treatments cancer patients received within 40 days before the onset of COVID-19 symptoms were radiotherapy (12.26%), chemotherapy (14.15%), surgery (7.62%), targeted therapies (3.81%), and immunotherapy (5.71%).

Compared with patients without cancer, those who received immunotherapy had a higher risk of:

• Severe/critical symptoms – OR, 10.61 (P < .01).
• Death – OR, 9.07 (P = .04).

Patients who underwent surgery had a higher risk of:

• Severe/critical symptoms – OR, 8.84 (P < .01).
• ICU admission – OR, 7.24 (P = .02).
• Invasive mechanical ventilation – OR, 44.33 (P < .01).

Conversely, outcomes in cancer patients who received radiotherapy were not significantly different from outcomes in patients without cancer (P > .10 for all).

These results suggest that “postponing surgery should be considered in outbreak areas,” Dr. Cai said, adding that scheduled radiotherapy can go ahead but with “intensive protection and surveillance.”

Dr. Cai said it remains to be seen whether patients with early-stage cancer need to postpone their treatments during the COVID-19 pandemic or whether immunotherapy aggravates severe outcomes in cancer patients with COVID-19. For now, she said, cancer patients should have individualized treatment plans based on their tumor type and stage.

Dr. Cai disclosed no conflicts of interest. This study was supported by the National Natural Science Foundation of China, the Singapore Ministry of Health’s National Medical Research Council, the National Institutes of Health/National Heart, Lung, and Blood Institute, and the Xiu Research Fund.

jensmith@mdedge.com

SOURCE: Cai H. AACR 2020. Patients with cancer appear more vulnerable to SARS-COV-2: A multicenter study during the COVID-19 outbreak; Dai M et al. Cancer Discov. 2020 Apr 28. doi: 10.1158/2159-8290.CD-20-0422.

The Food and Drug Administration has approved mitomycin pyelocalyceal (Jelmyto) as the first therapy for adults with low-grade upper tract urothelial cancer.

Olivier Le Moal/Getty Images

“This is the first approval specifically for patients with low-grade [upper tract urothelial cancer] and provides an option for some patients who may otherwise require a nephroureterectomy,” Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence, said in a statement.

“Due to substantial treatment challenges associated with the complex anatomy of the upper urinary tract, many patients need to be treated with radical surgery – usually complete removal of the affected kidney, ureter, and bladder cuff," Dr. Pazdur added. "Jelmyto gives patients, for the first time, an alternative treatment option for low-grade [upper tract urothelial cancer].”

The FDA’s approval of mitomycin is based on results from the phase 3 OLYMPUS trial (NCT02793128). This ongoing, single-arm trial enrolled 71 patients with treatment-naive or recurrent low-grade noninvasive upper tract urothelial cancer with at least one measurable papillary tumor located above the ureteropelvic junction. Patients with larger tumors were allowed to have prior tumor debulking.

The patients received mitomycin weekly for 6 weeks at the recommended dose of 4 mg/mL, instilled via ureteral catheter or nephrostomy tube, with the total instillation volume based on volumetric measurements using pyelography, not exceeding 15 mL (60 mg mitomycin).

Patients who achieved a complete response at 3 months could receive monthly instillations up to a maximum of 11 additional instillations.

At 3 months, 41 patients (58%) achieved a complete response (CR). At 12 months after CR determination, 19 patients were still in CR, and 7 patients had documented recurrences. The median duration of CR was not reached.

The most common adverse events (occurring in at least 20% of patients) were ureteric obstruction, flank pain, urinary tract infection, hematuria, renal dysfunction, fatigue, nausea, abdominal pain, dysuria, and vomiting. Ureteric obstruction occurred in 58% of patients, and 88% of those patients required ureteral stent placement.

In all, 23% of patients discontinued mitomycin due to adverse events, and 34% had dose interruptions due to adverse events.

The approval of mitomycin was granted to UroGen Pharma. The FDA granted the application priority review, fast track designation, and breakthrough therapy designation.

The full prescribing information for mitomycin is available for download from the FDA website.

jensmith@mdedge.com

The Food and Drug Administration has approved mitomycin pyelocalyceal (Jelmyto) as the first therapy for adults with low-grade upper tract urothelial cancer.

Olivier Le Moal/Getty Images

“This is the first approval specifically for patients with low-grade [upper tract urothelial cancer] and provides an option for some patients who may otherwise require a nephroureterectomy,” Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence, said in a statement.

“Due to substantial treatment challenges associated with the complex anatomy of the upper urinary tract, many patients need to be treated with radical surgery – usually complete removal of the affected kidney, ureter, and bladder cuff," Dr. Pazdur added. "Jelmyto gives patients, for the first time, an alternative treatment option for low-grade [upper tract urothelial cancer].”

The FDA’s approval of mitomycin is based on results from the phase 3 OLYMPUS trial (NCT02793128). This ongoing, single-arm trial enrolled 71 patients with treatment-naive or recurrent low-grade noninvasive upper tract urothelial cancer with at least one measurable papillary tumor located above the ureteropelvic junction. Patients with larger tumors were allowed to have prior tumor debulking.

The patients received mitomycin weekly for 6 weeks at the recommended dose of 4 mg/mL, instilled via ureteral catheter or nephrostomy tube, with the total instillation volume based on volumetric measurements using pyelography, not exceeding 15 mL (60 mg mitomycin).

Patients who achieved a complete response at 3 months could receive monthly instillations up to a maximum of 11 additional instillations.

At 3 months, 41 patients (58%) achieved a complete response (CR). At 12 months after CR determination, 19 patients were still in CR, and 7 patients had documented recurrences. The median duration of CR was not reached.

The most common adverse events (occurring in at least 20% of patients) were ureteric obstruction, flank pain, urinary tract infection, hematuria, renal dysfunction, fatigue, nausea, abdominal pain, dysuria, and vomiting. Ureteric obstruction occurred in 58% of patients, and 88% of those patients required ureteral stent placement.

In all, 23% of patients discontinued mitomycin due to adverse events, and 34% had dose interruptions due to adverse events.

The approval of mitomycin was granted to UroGen Pharma. The FDA granted the application priority review, fast track designation, and breakthrough therapy designation.

The full prescribing information for mitomycin is available for download from the FDA website.

jensmith@mdedge.com

The Food and Drug Administration has approved mitomycin pyelocalyceal (Jelmyto) as the first therapy for adults with low-grade upper tract urothelial cancer.

Olivier Le Moal/Getty Images

“This is the first approval specifically for patients with low-grade [upper tract urothelial cancer] and provides an option for some patients who may otherwise require a nephroureterectomy,” Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence, said in a statement.

“Due to substantial treatment challenges associated with the complex anatomy of the upper urinary tract, many patients need to be treated with radical surgery – usually complete removal of the affected kidney, ureter, and bladder cuff," Dr. Pazdur added. "Jelmyto gives patients, for the first time, an alternative treatment option for low-grade [upper tract urothelial cancer].”

The FDA’s approval of mitomycin is based on results from the phase 3 OLYMPUS trial (NCT02793128). This ongoing, single-arm trial enrolled 71 patients with treatment-naive or recurrent low-grade noninvasive upper tract urothelial cancer with at least one measurable papillary tumor located above the ureteropelvic junction. Patients with larger tumors were allowed to have prior tumor debulking.

The patients received mitomycin weekly for 6 weeks at the recommended dose of 4 mg/mL, instilled via ureteral catheter or nephrostomy tube, with the total instillation volume based on volumetric measurements using pyelography, not exceeding 15 mL (60 mg mitomycin).

Patients who achieved a complete response at 3 months could receive monthly instillations up to a maximum of 11 additional instillations.

At 3 months, 41 patients (58%) achieved a complete response (CR). At 12 months after CR determination, 19 patients were still in CR, and 7 patients had documented recurrences. The median duration of CR was not reached.

The most common adverse events (occurring in at least 20% of patients) were ureteric obstruction, flank pain, urinary tract infection, hematuria, renal dysfunction, fatigue, nausea, abdominal pain, dysuria, and vomiting. Ureteric obstruction occurred in 58% of patients, and 88% of those patients required ureteral stent placement.

In all, 23% of patients discontinued mitomycin due to adverse events, and 34% had dose interruptions due to adverse events.

The approval of mitomycin was granted to UroGen Pharma. The FDA granted the application priority review, fast track designation, and breakthrough therapy designation.

The full prescribing information for mitomycin is available for download from the FDA website.

jensmith@mdedge.com

A survey of gynecologic cancer survivors has revealed why some of these patients don’t participate in clinical trials.

Half of survey respondents with no history of trial participation said their medical team never mentioned the possibility of a trial. About 27% of respondents who never enrolled in a trial said they were interested in trial participation but didn’t qualify, the trial they wanted wasn’t available, their insurance didn’t cover participation, or the trial site was too far away.

Annie Ellis and Mary (Dicey) Jackson Scroggins, who are both ovarian cancer survivors and patient advocates, reported these findings in an abstract that had been slated for presentation at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer. The meeting was canceled because of the COVID-19 pandemic.

“We thought it was important to hear and learn directly from gynecologic cancer survivors,” Ms. Ellis said in an interview. “So we decided to conduct a survey that would expand knowledge about clinical trial participation from a gynecologic cancer patient–specific perspective.”

Ms. Ellis and Ms. Scroggins used survivor networks and social media to distribute a 26-question survey on trial participation. The survey was completed by 189 survivors of gynecologic cancers, 49.19% of whom experienced recurrent disease. The most common diagnoses were ovarian cancer (69.84%) and endometrial or uterine cancer (23.28%).
 

Perspectives of nonparticipants

Most respondents (65.61%) had never participated in a clinical trial. The most common reason was that the patient’s doctor or medical team never discussed trial participation (50.40%).

There were patients who were interested in trial participation but couldn’t enroll because they didn’t qualify (14.40%), the location was too far away (7.20%), the trial they wanted wasn’t available (4.00%), or their insurance didn’t cover trial participation (1.60%).

Patients who were not interested in trial participation said they didn’t want to receive a placebo (11.20%), they weren’t interested in experimental therapies (3.20%), or they didn’t want to be randomized (2.40%). One patient (1.60%) said she does not trust the medical system.

“Given the frequent conversations about distrust in the medical system, we were surprised that only 1 of the 189 respondents indicated distrust in the medical system as a reason for not participating in a clinical trial,” Ms. Ellis said.
 

Perspectives of trial participants

Roughly a third of respondents (34.39%) had participated in a clinical trial. Most (86.15%) said they learned about the trial from their doctor. Other sources included the patient’s own research (13.85%), a trial matching service (3.08%), a family member or friend (3.08%), and a support group (1.54%).

The most common reasons patients participated in trials were: “my doctor recommended it,” “to help women in the future,” “to expand my treatment options,” and “to have a chance to benefit personally.”

Additional responses indicated that patients viewed their trial participation in a positive light.

“We were surprised to find that 100% of the respondents who had participated in a clinical trial indicated either that they would participate again (84.62%) or that they were not sure about future participation (15.38%),” Ms. Ellis said. “No respondent indicated that she would not consider another trial. From open comments in the survey, it was clear that even if they did not obtain the result they hoped for or if the experience wasn’t optimal, they maintained the option of participating again.”
 

Implications and next steps

The survey results suggest there is a need for more discussions about clinical trials with patients who have gynecologic cancers, according to Ms. Ellis and Ms. Scroggins.

“We feel that conversations about clinical trials, with health care team members, should be included at every care decision point, even if – or perhaps especially if – the patient belongs to a group perceived to be unlikely to agree to participate in a trial,” Ms. Ellis said.

“These conversations are necessary with all patients-survivors,” she said, “but they are particularly important and necessary with patients from populations underrepresented in the clinical trial system if we want more representative trial populations, more generalizable results, and the potential for better outcomes for all.”

For their part, Ms. Ellis and Ms. Scroggins plan to conduct more research on this topic to gain additional insights.

“We’d like to conduct a larger survey looking deeper into barriers to and reasons for participation, and to work with medical professionals to develop models of communication to encourage consideration of clinical trials,” Ms. Ellis said. “Additionally, we will work to have a more diverse respondent pool across many dimensions.”

Ms. Ellis is a research advocate on the scientific advisory committee of the Ovarian Cancer National Alliance in Washington. Ms. Scroggins is the director of global outreach and engagement at the International Gynecologic Cancer Society in Louisville, Ken. They have no conflicts of interest.

jensmith@mdedge.com

SOURCE: Ellis A and Scroggins MJ. SGO 2020, Abstract 540.

A survey of gynecologic cancer survivors has revealed why some of these patients don’t participate in clinical trials.

Half of survey respondents with no history of trial participation said their medical team never mentioned the possibility of a trial. About 27% of respondents who never enrolled in a trial said they were interested in trial participation but didn’t qualify, the trial they wanted wasn’t available, their insurance didn’t cover participation, or the trial site was too far away.

Annie Ellis and Mary (Dicey) Jackson Scroggins, who are both ovarian cancer survivors and patient advocates, reported these findings in an abstract that had been slated for presentation at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer. The meeting was canceled because of the COVID-19 pandemic.

“We thought it was important to hear and learn directly from gynecologic cancer survivors,” Ms. Ellis said in an interview. “So we decided to conduct a survey that would expand knowledge about clinical trial participation from a gynecologic cancer patient–specific perspective.”

Ms. Ellis and Ms. Scroggins used survivor networks and social media to distribute a 26-question survey on trial participation. The survey was completed by 189 survivors of gynecologic cancers, 49.19% of whom experienced recurrent disease. The most common diagnoses were ovarian cancer (69.84%) and endometrial or uterine cancer (23.28%).
 

Perspectives of nonparticipants

Most respondents (65.61%) had never participated in a clinical trial. The most common reason was that the patient’s doctor or medical team never discussed trial participation (50.40%).

There were patients who were interested in trial participation but couldn’t enroll because they didn’t qualify (14.40%), the location was too far away (7.20%), the trial they wanted wasn’t available (4.00%), or their insurance didn’t cover trial participation (1.60%).

Patients who were not interested in trial participation said they didn’t want to receive a placebo (11.20%), they weren’t interested in experimental therapies (3.20%), or they didn’t want to be randomized (2.40%). One patient (1.60%) said she does not trust the medical system.

“Given the frequent conversations about distrust in the medical system, we were surprised that only 1 of the 189 respondents indicated distrust in the medical system as a reason for not participating in a clinical trial,” Ms. Ellis said.
 

Perspectives of trial participants

Roughly a third of respondents (34.39%) had participated in a clinical trial. Most (86.15%) said they learned about the trial from their doctor. Other sources included the patient’s own research (13.85%), a trial matching service (3.08%), a family member or friend (3.08%), and a support group (1.54%).

The most common reasons patients participated in trials were: “my doctor recommended it,” “to help women in the future,” “to expand my treatment options,” and “to have a chance to benefit personally.”

Additional responses indicated that patients viewed their trial participation in a positive light.

“We were surprised to find that 100% of the respondents who had participated in a clinical trial indicated either that they would participate again (84.62%) or that they were not sure about future participation (15.38%),” Ms. Ellis said. “No respondent indicated that she would not consider another trial. From open comments in the survey, it was clear that even if they did not obtain the result they hoped for or if the experience wasn’t optimal, they maintained the option of participating again.”
 

Implications and next steps

The survey results suggest there is a need for more discussions about clinical trials with patients who have gynecologic cancers, according to Ms. Ellis and Ms. Scroggins.

“We feel that conversations about clinical trials, with health care team members, should be included at every care decision point, even if – or perhaps especially if – the patient belongs to a group perceived to be unlikely to agree to participate in a trial,” Ms. Ellis said.

“These conversations are necessary with all patients-survivors,” she said, “but they are particularly important and necessary with patients from populations underrepresented in the clinical trial system if we want more representative trial populations, more generalizable results, and the potential for better outcomes for all.”

For their part, Ms. Ellis and Ms. Scroggins plan to conduct more research on this topic to gain additional insights.

“We’d like to conduct a larger survey looking deeper into barriers to and reasons for participation, and to work with medical professionals to develop models of communication to encourage consideration of clinical trials,” Ms. Ellis said. “Additionally, we will work to have a more diverse respondent pool across many dimensions.”

Ms. Ellis is a research advocate on the scientific advisory committee of the Ovarian Cancer National Alliance in Washington. Ms. Scroggins is the director of global outreach and engagement at the International Gynecologic Cancer Society in Louisville, Ken. They have no conflicts of interest.

jensmith@mdedge.com

SOURCE: Ellis A and Scroggins MJ. SGO 2020, Abstract 540.

A survey of gynecologic cancer survivors has revealed why some of these patients don’t participate in clinical trials.

Half of survey respondents with no history of trial participation said their medical team never mentioned the possibility of a trial. About 27% of respondents who never enrolled in a trial said they were interested in trial participation but didn’t qualify, the trial they wanted wasn’t available, their insurance didn’t cover participation, or the trial site was too far away.

Annie Ellis and Mary (Dicey) Jackson Scroggins, who are both ovarian cancer survivors and patient advocates, reported these findings in an abstract that had been slated for presentation at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer. The meeting was canceled because of the COVID-19 pandemic.

“We thought it was important to hear and learn directly from gynecologic cancer survivors,” Ms. Ellis said in an interview. “So we decided to conduct a survey that would expand knowledge about clinical trial participation from a gynecologic cancer patient–specific perspective.”

Ms. Ellis and Ms. Scroggins used survivor networks and social media to distribute a 26-question survey on trial participation. The survey was completed by 189 survivors of gynecologic cancers, 49.19% of whom experienced recurrent disease. The most common diagnoses were ovarian cancer (69.84%) and endometrial or uterine cancer (23.28%).
 

Perspectives of nonparticipants

Most respondents (65.61%) had never participated in a clinical trial. The most common reason was that the patient’s doctor or medical team never discussed trial participation (50.40%).

There were patients who were interested in trial participation but couldn’t enroll because they didn’t qualify (14.40%), the location was too far away (7.20%), the trial they wanted wasn’t available (4.00%), or their insurance didn’t cover trial participation (1.60%).

Patients who were not interested in trial participation said they didn’t want to receive a placebo (11.20%), they weren’t interested in experimental therapies (3.20%), or they didn’t want to be randomized (2.40%). One patient (1.60%) said she does not trust the medical system.

“Given the frequent conversations about distrust in the medical system, we were surprised that only 1 of the 189 respondents indicated distrust in the medical system as a reason for not participating in a clinical trial,” Ms. Ellis said.
 

Perspectives of trial participants

Roughly a third of respondents (34.39%) had participated in a clinical trial. Most (86.15%) said they learned about the trial from their doctor. Other sources included the patient’s own research (13.85%), a trial matching service (3.08%), a family member or friend (3.08%), and a support group (1.54%).

The most common reasons patients participated in trials were: “my doctor recommended it,” “to help women in the future,” “to expand my treatment options,” and “to have a chance to benefit personally.”

Additional responses indicated that patients viewed their trial participation in a positive light.

“We were surprised to find that 100% of the respondents who had participated in a clinical trial indicated either that they would participate again (84.62%) or that they were not sure about future participation (15.38%),” Ms. Ellis said. “No respondent indicated that she would not consider another trial. From open comments in the survey, it was clear that even if they did not obtain the result they hoped for or if the experience wasn’t optimal, they maintained the option of participating again.”
 

Implications and next steps

The survey results suggest there is a need for more discussions about clinical trials with patients who have gynecologic cancers, according to Ms. Ellis and Ms. Scroggins.

“We feel that conversations about clinical trials, with health care team members, should be included at every care decision point, even if – or perhaps especially if – the patient belongs to a group perceived to be unlikely to agree to participate in a trial,” Ms. Ellis said.

“These conversations are necessary with all patients-survivors,” she said, “but they are particularly important and necessary with patients from populations underrepresented in the clinical trial system if we want more representative trial populations, more generalizable results, and the potential for better outcomes for all.”

For their part, Ms. Ellis and Ms. Scroggins plan to conduct more research on this topic to gain additional insights.

“We’d like to conduct a larger survey looking deeper into barriers to and reasons for participation, and to work with medical professionals to develop models of communication to encourage consideration of clinical trials,” Ms. Ellis said. “Additionally, we will work to have a more diverse respondent pool across many dimensions.”

Ms. Ellis is a research advocate on the scientific advisory committee of the Ovarian Cancer National Alliance in Washington. Ms. Scroggins is the director of global outreach and engagement at the International Gynecologic Cancer Society in Louisville, Ken. They have no conflicts of interest.

jensmith@mdedge.com

SOURCE: Ellis A and Scroggins MJ. SGO 2020, Abstract 540.

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.

A small molecule can provide a “clinically meaningful reduction” in severe oral mucositis without affecting tumor control in head and neck cancer, according to an investigator from a phase 2 trial.

The molecule, GC4419 (avasopasem manganese), is designed to convert superoxide to hydrogen peroxide and oxygen, thereby protecting normal tissue from damage associated with radiotherapy.

Investigators tested GC4419 in a phase 2 trial of patients with locally advanced oral cavity or oropharynx cancer who received intensity-modulated radiotherapy plus cisplatin. Initial results from this trial were published in December (J Clin Oncol. 2019 Dec 1;37[34]:3256-65).

Carryn M. Anderson, MD, of University of Iowa Hospitals & Clinics in Iowa City, presented updated results at the Multidisciplinary Head and Neck Cancer Symposium, sponsored by the American Society for Radiation Oncology.

The trial (NCT02508389) enrolled 223 patients scheduled to be treated with intensity-modulated radiotherapy (60-72 Gy or greater than 50 Gy to more than two oral sites) plus cisplatin (weekly or every 3 weeks).

The patients were randomized to receive 30 mg of GC4419 (n = 73), 90 mg of GC4419 (n = 76), or placebo (n = 74) intravenously over 60 minutes prior to each radiotherapy fraction. Baseline patient and tumor characteristics were well balanced among the treatment arms.
 

Efficacy and safety

The study’s primary endpoint was the duration of severe oral mucositis. When compared with placebo, the 90-mg dose of GC4419 conferred a 92% reduction in median days of severe oral mucositis (P = .024).

The 90-mg dose of GC4419 also reduced the incidence of severe oral mucositis by 34% (P = .009) and the rate of grade 4 oral mucositis by 47% (P = .045) when compared with placebo.

“GC4419, particularly the 90-mg dosage, provides a clinically meaningful reduction in severe oral mucositis duration, incidence, and severity,” Dr. Anderson noted.

“Safety was comparable across study arms,” she added. “The most frequent adverse events were those already expected with cisplatin and radiation, and those were not worsened in any way by the addition of this drug.”

Adverse events expected with GC4419 were “mild and transient,” according to Dr. Anderson. These events included syncope, hypotension/orthostasis, and oral/facial paresthesia.

Grade 3 syncope occurred in 4% of patients in the placebo arm, 4% in the 30-mg arm, and 6% in the 90-mg arm. Grade 3 hypotension/orthostasis occurred in 6%, 4%, and 4%, respectively. Grade 1 oral/facial paresthesia occurred in 15%, 10%, and 19%, respectively.
 

Long-term outcomes

“The 1- and 2-year tumor control is similar with utilization of [GC4419], and this is consistent with the drug’s known mechanism and previous animal models,” Dr. Anderson said.

At 1 and 2 years, there were no significant differences between the treatment arms with regard to locoregional control, distant metastasis, progression-free survival, or overall survival.

The 1-year progression-free survival was 82% in the placebo arm, 86% in the 30-mg arm, and 80% in the 90-mg arm. The 1-year overall survival was 93%, 91%, and 88%, respectively.

The 2-year progression-free survival was 77% in the placebo arm, 76% in the 30-mg arm, and 77% in the 90-mg arm. The 1-year overall survival was 87%, 85%, and 86%, respectively.
 

From trials to practice

Despite the favorable results of this trial, meeting attendees expressed concerns that the administration of GC4419 may not be feasible in real-life because it is labor- and resource-intensive.

“Methodologically, the study was excellent,” said attendee Shahid Iqbal, MBBS, a consultant clinical oncologist at Newcastle upon Tyne Hospitals NHS Foundation Trust in the United Kingdom, who was not involved in this trial.

Dr. Iqbal noted that this placebo-controlled trial had a “very reasonable number of patients in each arm,” the 90-mg dose of GC4419 was “effective,” and the drug had “no adverse impact on survival.”

“However, in my personal opinion, this intravenous infusion on a daily basis is not feasible in real life,” Dr. Iqbal said. “I cannot see this becoming a standard of care in National Health Service UK. This is simply not cost-effective at all.”

Although she didn’t address costs, Dr. Anderson did acknowledge that administering GC4419 is labor intensive.

“But we are hopeful that, if this drug ultimately makes it to [Food and Drug Administration] approval, the efficacy benefits we are showing will make the work flow changes worthwhile,” she said. “We certainly have shown that, in this study, 44 institutions could make that happen. At the University of Iowa, we found it easiest to institute an infusion space within the department of radiation oncology rather than relying on our medical oncology colleagues to let us borrow a chair.”

GC4419 is now under investigation in a phase 3 trial (NCT03689712) and has received fast track and breakthrough therapy designations from the FDA.

The phase 2 trial was sponsored by Galera Therapeutics. Dr. Anderson is an uncompensated research adviser to the company. Dr. Iqbal has no relevant conflicts of interest.

jensmith@mdedge.com

SOURCE: Anderson CM et al. Head and Neck Cancer Symposium. Abstract LBA 2.

A small molecule can provide a “clinically meaningful reduction” in severe oral mucositis without affecting tumor control in head and neck cancer, according to an investigator from a phase 2 trial.

The molecule, GC4419 (avasopasem manganese), is designed to convert superoxide to hydrogen peroxide and oxygen, thereby protecting normal tissue from damage associated with radiotherapy.

Investigators tested GC4419 in a phase 2 trial of patients with locally advanced oral cavity or oropharynx cancer who received intensity-modulated radiotherapy plus cisplatin. Initial results from this trial were published in December (J Clin Oncol. 2019 Dec 1;37[34]:3256-65).

Carryn M. Anderson, MD, of University of Iowa Hospitals & Clinics in Iowa City, presented updated results at the Multidisciplinary Head and Neck Cancer Symposium, sponsored by the American Society for Radiation Oncology.

The trial (NCT02508389) enrolled 223 patients scheduled to be treated with intensity-modulated radiotherapy (60-72 Gy or greater than 50 Gy to more than two oral sites) plus cisplatin (weekly or every 3 weeks).

The patients were randomized to receive 30 mg of GC4419 (n = 73), 90 mg of GC4419 (n = 76), or placebo (n = 74) intravenously over 60 minutes prior to each radiotherapy fraction. Baseline patient and tumor characteristics were well balanced among the treatment arms.
 

Efficacy and safety

The study’s primary endpoint was the duration of severe oral mucositis. When compared with placebo, the 90-mg dose of GC4419 conferred a 92% reduction in median days of severe oral mucositis (P = .024).

The 90-mg dose of GC4419 also reduced the incidence of severe oral mucositis by 34% (P = .009) and the rate of grade 4 oral mucositis by 47% (P = .045) when compared with placebo.

“GC4419, particularly the 90-mg dosage, provides a clinically meaningful reduction in severe oral mucositis duration, incidence, and severity,” Dr. Anderson noted.

“Safety was comparable across study arms,” she added. “The most frequent adverse events were those already expected with cisplatin and radiation, and those were not worsened in any way by the addition of this drug.”

Adverse events expected with GC4419 were “mild and transient,” according to Dr. Anderson. These events included syncope, hypotension/orthostasis, and oral/facial paresthesia.

Grade 3 syncope occurred in 4% of patients in the placebo arm, 4% in the 30-mg arm, and 6% in the 90-mg arm. Grade 3 hypotension/orthostasis occurred in 6%, 4%, and 4%, respectively. Grade 1 oral/facial paresthesia occurred in 15%, 10%, and 19%, respectively.
 

Long-term outcomes

“The 1- and 2-year tumor control is similar with utilization of [GC4419], and this is consistent with the drug’s known mechanism and previous animal models,” Dr. Anderson said.

At 1 and 2 years, there were no significant differences between the treatment arms with regard to locoregional control, distant metastasis, progression-free survival, or overall survival.

The 1-year progression-free survival was 82% in the placebo arm, 86% in the 30-mg arm, and 80% in the 90-mg arm. The 1-year overall survival was 93%, 91%, and 88%, respectively.

The 2-year progression-free survival was 77% in the placebo arm, 76% in the 30-mg arm, and 77% in the 90-mg arm. The 1-year overall survival was 87%, 85%, and 86%, respectively.
 

From trials to practice

Despite the favorable results of this trial, meeting attendees expressed concerns that the administration of GC4419 may not be feasible in real-life because it is labor- and resource-intensive.

“Methodologically, the study was excellent,” said attendee Shahid Iqbal, MBBS, a consultant clinical oncologist at Newcastle upon Tyne Hospitals NHS Foundation Trust in the United Kingdom, who was not involved in this trial.

Dr. Iqbal noted that this placebo-controlled trial had a “very reasonable number of patients in each arm,” the 90-mg dose of GC4419 was “effective,” and the drug had “no adverse impact on survival.”

“However, in my personal opinion, this intravenous infusion on a daily basis is not feasible in real life,” Dr. Iqbal said. “I cannot see this becoming a standard of care in National Health Service UK. This is simply not cost-effective at all.”

Although she didn’t address costs, Dr. Anderson did acknowledge that administering GC4419 is labor intensive.

“But we are hopeful that, if this drug ultimately makes it to [Food and Drug Administration] approval, the efficacy benefits we are showing will make the work flow changes worthwhile,” she said. “We certainly have shown that, in this study, 44 institutions could make that happen. At the University of Iowa, we found it easiest to institute an infusion space within the department of radiation oncology rather than relying on our medical oncology colleagues to let us borrow a chair.”

GC4419 is now under investigation in a phase 3 trial (NCT03689712) and has received fast track and breakthrough therapy designations from the FDA.

The phase 2 trial was sponsored by Galera Therapeutics. Dr. Anderson is an uncompensated research adviser to the company. Dr. Iqbal has no relevant conflicts of interest.

jensmith@mdedge.com

SOURCE: Anderson CM et al. Head and Neck Cancer Symposium. Abstract LBA 2.

A small molecule can provide a “clinically meaningful reduction” in severe oral mucositis without affecting tumor control in head and neck cancer, according to an investigator from a phase 2 trial.

The molecule, GC4419 (avasopasem manganese), is designed to convert superoxide to hydrogen peroxide and oxygen, thereby protecting normal tissue from damage associated with radiotherapy.

Investigators tested GC4419 in a phase 2 trial of patients with locally advanced oral cavity or oropharynx cancer who received intensity-modulated radiotherapy plus cisplatin. Initial results from this trial were published in December (J Clin Oncol. 2019 Dec 1;37[34]:3256-65).

Carryn M. Anderson, MD, of University of Iowa Hospitals & Clinics in Iowa City, presented updated results at the Multidisciplinary Head and Neck Cancer Symposium, sponsored by the American Society for Radiation Oncology.

The trial (NCT02508389) enrolled 223 patients scheduled to be treated with intensity-modulated radiotherapy (60-72 Gy or greater than 50 Gy to more than two oral sites) plus cisplatin (weekly or every 3 weeks).

The patients were randomized to receive 30 mg of GC4419 (n = 73), 90 mg of GC4419 (n = 76), or placebo (n = 74) intravenously over 60 minutes prior to each radiotherapy fraction. Baseline patient and tumor characteristics were well balanced among the treatment arms.
 

Efficacy and safety

The study’s primary endpoint was the duration of severe oral mucositis. When compared with placebo, the 90-mg dose of GC4419 conferred a 92% reduction in median days of severe oral mucositis (P = .024).

The 90-mg dose of GC4419 also reduced the incidence of severe oral mucositis by 34% (P = .009) and the rate of grade 4 oral mucositis by 47% (P = .045) when compared with placebo.

“GC4419, particularly the 90-mg dosage, provides a clinically meaningful reduction in severe oral mucositis duration, incidence, and severity,” Dr. Anderson noted.

“Safety was comparable across study arms,” she added. “The most frequent adverse events were those already expected with cisplatin and radiation, and those were not worsened in any way by the addition of this drug.”

Adverse events expected with GC4419 were “mild and transient,” according to Dr. Anderson. These events included syncope, hypotension/orthostasis, and oral/facial paresthesia.

Grade 3 syncope occurred in 4% of patients in the placebo arm, 4% in the 30-mg arm, and 6% in the 90-mg arm. Grade 3 hypotension/orthostasis occurred in 6%, 4%, and 4%, respectively. Grade 1 oral/facial paresthesia occurred in 15%, 10%, and 19%, respectively.
 

Long-term outcomes

“The 1- and 2-year tumor control is similar with utilization of [GC4419], and this is consistent with the drug’s known mechanism and previous animal models,” Dr. Anderson said.

At 1 and 2 years, there were no significant differences between the treatment arms with regard to locoregional control, distant metastasis, progression-free survival, or overall survival.

The 1-year progression-free survival was 82% in the placebo arm, 86% in the 30-mg arm, and 80% in the 90-mg arm. The 1-year overall survival was 93%, 91%, and 88%, respectively.

The 2-year progression-free survival was 77% in the placebo arm, 76% in the 30-mg arm, and 77% in the 90-mg arm. The 1-year overall survival was 87%, 85%, and 86%, respectively.
 

From trials to practice

Despite the favorable results of this trial, meeting attendees expressed concerns that the administration of GC4419 may not be feasible in real-life because it is labor- and resource-intensive.

“Methodologically, the study was excellent,” said attendee Shahid Iqbal, MBBS, a consultant clinical oncologist at Newcastle upon Tyne Hospitals NHS Foundation Trust in the United Kingdom, who was not involved in this trial.

Dr. Iqbal noted that this placebo-controlled trial had a “very reasonable number of patients in each arm,” the 90-mg dose of GC4419 was “effective,” and the drug had “no adverse impact on survival.”

“However, in my personal opinion, this intravenous infusion on a daily basis is not feasible in real life,” Dr. Iqbal said. “I cannot see this becoming a standard of care in National Health Service UK. This is simply not cost-effective at all.”

Although she didn’t address costs, Dr. Anderson did acknowledge that administering GC4419 is labor intensive.

“But we are hopeful that, if this drug ultimately makes it to [Food and Drug Administration] approval, the efficacy benefits we are showing will make the work flow changes worthwhile,” she said. “We certainly have shown that, in this study, 44 institutions could make that happen. At the University of Iowa, we found it easiest to institute an infusion space within the department of radiation oncology rather than relying on our medical oncology colleagues to let us borrow a chair.”

GC4419 is now under investigation in a phase 3 trial (NCT03689712) and has received fast track and breakthrough therapy designations from the FDA.

The phase 2 trial was sponsored by Galera Therapeutics. Dr. Anderson is an uncompensated research adviser to the company. Dr. Iqbal has no relevant conflicts of interest.

jensmith@mdedge.com

SOURCE: Anderson CM et al. Head and Neck Cancer Symposium. Abstract LBA 2.

The International Association for the Study of Lung Cancer (IASLC) is naming the Translational Research Lectureship Award after Fred R. Hirsch, MD, PhD, of the Tisch Cancer Institute and Icahn School of Medicine at Mount Sinai, New York.

Dr. Hirsch was a longtime member of the IASLC and served as chief executive officer of the association from 2013 through October 2018. During this time, Dr. Hirsch grew the IASLC staff from 5 to 23 people and doubled the organization’s membership. The IASLC World Conference on Lung Cancer became an annual meeting under Dr. Hirsch’s direction and reported record attendance, according to their website.

The recipient of the Fred R. Hirsch Lectureship Award for Translational Research will be recognized at the IASLC 2020 World Conference on Lung Cancer, which is set to take place in Singapore on August 9-12, 2020.

In other news, the American Cancer Society (ACS) announced that it has awarded the 2020 Medal of Honor to three researchers. The recipients will be recognized at a black-tie ceremony in New York on Nov. 11, 2020.

Lewis C. Cantley, PhD, of Weill Cornell Medicine, New York, won the Medal of Honor for Basic Research. This award honors researchers whose work will have a “lasting impact on the cancer field” or who have made important discoveries or inventions within the field, according to the ACS.

Dr. Cantley won the award for research that has improved our understanding of cancer metabolism. He is known for his contributions to the discovery and study of phosphoinositide 3-kinase, which plays a role in many cancers and has become a target for therapies.

Leslie Bernstein, PhD, of City of Hope National Medical Center in Duarte, Calif., has won the Medal of Honor in Cancer Control. This award honors individuals who have made strides in public health, public communication, or public policy that have had an impact on cancer control.

Dr. Bernstein won the award for her work linking physical activity to a reduced risk of breast cancer. She is currently investigating links between hormone exposures, physical activity, obesity, and cancer, as well as examining how breast cancer impacts patients’ lives after treatment.

Ching-Hon Pui, MD, of St. Jude Children’s Research Hospital in Memphis, Tenn., has won the Medal of Honor in Clinical Research. This award honors researchers whose work has significantly improved cancer patients’ outcomes.

Dr. Pui won the award for his work in childhood acute lymphoblastic leukemia. Dr. Pui’s work has led to increased global treatment access, improved survival rates, and better quality of life for patients with childhood acute lymphoblastic leukemia.

jensmith@mdedge.com

The International Association for the Study of Lung Cancer (IASLC) is naming the Translational Research Lectureship Award after Fred R. Hirsch, MD, PhD, of the Tisch Cancer Institute and Icahn School of Medicine at Mount Sinai, New York.

Dr. Hirsch was a longtime member of the IASLC and served as chief executive officer of the association from 2013 through October 2018. During this time, Dr. Hirsch grew the IASLC staff from 5 to 23 people and doubled the organization’s membership. The IASLC World Conference on Lung Cancer became an annual meeting under Dr. Hirsch’s direction and reported record attendance, according to their website.

The recipient of the Fred R. Hirsch Lectureship Award for Translational Research will be recognized at the IASLC 2020 World Conference on Lung Cancer, which is set to take place in Singapore on August 9-12, 2020.

In other news, the American Cancer Society (ACS) announced that it has awarded the 2020 Medal of Honor to three researchers. The recipients will be recognized at a black-tie ceremony in New York on Nov. 11, 2020.

Lewis C. Cantley, PhD, of Weill Cornell Medicine, New York, won the Medal of Honor for Basic Research. This award honors researchers whose work will have a “lasting impact on the cancer field” or who have made important discoveries or inventions within the field, according to the ACS.

Dr. Cantley won the award for research that has improved our understanding of cancer metabolism. He is known for his contributions to the discovery and study of phosphoinositide 3-kinase, which plays a role in many cancers and has become a target for therapies.

Leslie Bernstein, PhD, of City of Hope National Medical Center in Duarte, Calif., has won the Medal of Honor in Cancer Control. This award honors individuals who have made strides in public health, public communication, or public policy that have had an impact on cancer control.

Dr. Bernstein won the award for her work linking physical activity to a reduced risk of breast cancer. She is currently investigating links between hormone exposures, physical activity, obesity, and cancer, as well as examining how breast cancer impacts patients’ lives after treatment.

Ching-Hon Pui, MD, of St. Jude Children’s Research Hospital in Memphis, Tenn., has won the Medal of Honor in Clinical Research. This award honors researchers whose work has significantly improved cancer patients’ outcomes.

Dr. Pui won the award for his work in childhood acute lymphoblastic leukemia. Dr. Pui’s work has led to increased global treatment access, improved survival rates, and better quality of life for patients with childhood acute lymphoblastic leukemia.

jensmith@mdedge.com

The International Association for the Study of Lung Cancer (IASLC) is naming the Translational Research Lectureship Award after Fred R. Hirsch, MD, PhD, of the Tisch Cancer Institute and Icahn School of Medicine at Mount Sinai, New York.

Dr. Hirsch was a longtime member of the IASLC and served as chief executive officer of the association from 2013 through October 2018. During this time, Dr. Hirsch grew the IASLC staff from 5 to 23 people and doubled the organization’s membership. The IASLC World Conference on Lung Cancer became an annual meeting under Dr. Hirsch’s direction and reported record attendance, according to their website.

The recipient of the Fred R. Hirsch Lectureship Award for Translational Research will be recognized at the IASLC 2020 World Conference on Lung Cancer, which is set to take place in Singapore on August 9-12, 2020.

In other news, the American Cancer Society (ACS) announced that it has awarded the 2020 Medal of Honor to three researchers. The recipients will be recognized at a black-tie ceremony in New York on Nov. 11, 2020.

Lewis C. Cantley, PhD, of Weill Cornell Medicine, New York, won the Medal of Honor for Basic Research. This award honors researchers whose work will have a “lasting impact on the cancer field” or who have made important discoveries or inventions within the field, according to the ACS.

Dr. Cantley won the award for research that has improved our understanding of cancer metabolism. He is known for his contributions to the discovery and study of phosphoinositide 3-kinase, which plays a role in many cancers and has become a target for therapies.

Leslie Bernstein, PhD, of City of Hope National Medical Center in Duarte, Calif., has won the Medal of Honor in Cancer Control. This award honors individuals who have made strides in public health, public communication, or public policy that have had an impact on cancer control.

Dr. Bernstein won the award for her work linking physical activity to a reduced risk of breast cancer. She is currently investigating links between hormone exposures, physical activity, obesity, and cancer, as well as examining how breast cancer impacts patients’ lives after treatment.

Ching-Hon Pui, MD, of St. Jude Children’s Research Hospital in Memphis, Tenn., has won the Medal of Honor in Clinical Research. This award honors researchers whose work has significantly improved cancer patients’ outcomes.

Dr. Pui won the award for his work in childhood acute lymphoblastic leukemia. Dr. Pui’s work has led to increased global treatment access, improved survival rates, and better quality of life for patients with childhood acute lymphoblastic leukemia.

jensmith@mdedge.com

Adding cetuximab to radiotherapy and cisplatin does not improve outcomes in patients with locoregionally advanced head and neck carcinoma, according to 10-year follow-up from a phase 3 trial.

The addition of cetuximab did not reduce local-regional failure or distant metastasis, and it did not improve progression-free or overall survival.

“With a median follow-up of over 10 years, this updated report confirms the addition of cetuximab to radiation/cisplatin did not improve any measured outcome in the entire cohort or when stratifying by p16 status,” said Jimmy J. Caudell, MD, of Moffitt Cancer Center in Tampa, Fla.

Dr. Caudell presented this update at the Multidisciplinary Head and Neck Cancer Symposium, sponsored by the American Society for Radiation Oncology.

Dr. Caudell noted that cisplatin plus radiotherapy or cetuximab plus radiotherapy have been shown to improve overall survival in patients with locoregionally advanced head and neck carcinoma. Researchers conducted this phase 3 trial, RTOG 0522 (NCT00265941), to determine if adding cetuximab to radiotherapy and cisplatin would improve progression-free survival.

The trial included 891 evaluable patients with stage T2 N2a-3 M0 or T3-4 N0-3 M0 disease. They were randomized to receive radiotherapy and cisplatin without cetuximab (n = 447) or with cetuximab (n = 444). Most patients were assigned to intensity-modulated radiotherapy (86.8% in the radiotherapy/cisplatin arm and 89.2% in the cetuximab arm) rather than 3-D conformal radiotherapy (13.2% and 10.8%, respectively).

Baseline characteristics were balanced between the treatment arms. The median age was 57 years (range, 31-79 years) in the radiotherapy/cisplatin arm and 58 years (range, 34-76 years) in the cetuximab arm. Nearly 90% of patients in both arms were men, and the oropharynx was the primary site of disease in about 70% of patients in both arms.

More patients were p16-positive (35.7% in the radiotherapy/cisplatin arm and 39.4% in the cetuximab arm) than were p16-negative (14.4% and 13.1%, respectively). However, p16 status was unknown for about half of patients in each arm.
 

Long-term efficacy

At a median follow-up of 10.1 years, 452 patients were still alive.

The rate of local-regional failure was 28.5% in the radiotherapy/cisplatin arm and 34.8% in the cetuximab arm (hazard ratio, 1.21; P = .94). The rate of distant metastases was 15% and 11.8%, respectively (HR, 0.79; P = .10).

The 10-year progression-free survival rate was 43.6% in the radiotherapy/cisplatin arm and 40.2% in the cetuximab arm (HR, 1.06; P = .74). The 10-year overall survival rate was 49.9% and 50%, respectively (HR, 0.97; P = .36)

“As might be expected, patients who were p16-positive had a substantially improved progression-free survival as well as overall survival,” Dr. Caudell said. “Patients who had p16-negative oropharyngeal cancer or nonoropharyngeal cancer had equivalent progression-free survival and overall survival.”

However, the addition of cetuximab did not improve progression-free or overall survival in patients with p16-positive, p16-negative oropharyngeal, or nonoropharyngeal cancers.

“[These results] have proven conclusively that the addition of cetuximab to concurrent cisplatin and radiation therapy does not improve outcomes in stage III-IV head and neck cancer, regardless of the primary tumor site and p16 status,” said Kartik Sehgal, MD, of Beth Israel Deaconess Medical Center in Boston, who was not involved in this study.
 

Late toxicity

Dr. Caudell noted that late toxicity was “substantial” in both treatment arms. Late toxicity was defined as adverse events occurring greater than 90 days from the start of radiotherapy.

The incidence of grade 3/4 late toxicity was 57.4% in the radiotherapy/cisplatin arm and 61.3% in the cetuximab arm (P = .26). The most common grade 3/4 late adverse event was dysphagia, occurring in 39.6% of patients in the radiotherapy/cisplatin arm and 38.2% of those in the cetuximab arm.

Other late grade 3/4 events (in the radiotherapy/cisplatin and cetuximab arms, respectively) included dry mouth (3% and 5%), radiation mucositis (5.3% and 7%), weight decrease (7.6% and 8.7%), hearing impairment (6% and 5%), pharynx mucositis/stomatitis (4.9% and 6%), and osteonecrosis (6% and 4.8%).

Feeding tube use was similar in both treatment arms over time. At 10 years, 14.3% of patients in the radiotherapy/cisplatin arm and 11% of those in the cetuximab arm used a feeding tube (P = .53).

“Despite the use of intensity-modulated radiotherapy, there was a high incidence of late grade 3 and higher toxicities, primarily related to dysphagia, which have substantial effects on the quality of life of our patients,” Dr. Sehgal noted. “These findings need to be considered carefully while designing future studies.

“Future directions for the management of locoregionally advanced head and neck cancer include evaluation of benefits from the addition of immune checkpoint inhibitors to cisplatin with concurrent radiation therapy (e.g., JAVELIN with avelumab [NCT01772004], KEYNOTE-412 with pembrolizumab [NCT03040999], and NCT03349710 with nivolumab) and whether immune checkpoint inhibitors can substitute for cisplatin in those being treated concurrently with radiation therapy (e.g., REACH trial comparing avelumab, cetuximab, and radiation therapy versus cisplatin plus radiation therapy [NCT02999087]).”

The current study was sponsored by the Radiation Therapy Oncology Group, the National Cancer Institute, NRG Oncology, and Eli Lilly. Dr. Caudell disclosed grants and fees from Varian Medical Systems. Dr. Sehgal had no conflicts of interest to disclose.

jensmith@mdedge.com

SOURCE: Caudell J et al. Head and Neck Cancers Symposium 2020, Abstract 6.

Adding cetuximab to radiotherapy and cisplatin does not improve outcomes in patients with locoregionally advanced head and neck carcinoma, according to 10-year follow-up from a phase 3 trial.

The addition of cetuximab did not reduce local-regional failure or distant metastasis, and it did not improve progression-free or overall survival.

“With a median follow-up of over 10 years, this updated report confirms the addition of cetuximab to radiation/cisplatin did not improve any measured outcome in the entire cohort or when stratifying by p16 status,” said Jimmy J. Caudell, MD, of Moffitt Cancer Center in Tampa, Fla.

Dr. Caudell presented this update at the Multidisciplinary Head and Neck Cancer Symposium, sponsored by the American Society for Radiation Oncology.

Dr. Caudell noted that cisplatin plus radiotherapy or cetuximab plus radiotherapy have been shown to improve overall survival in patients with locoregionally advanced head and neck carcinoma. Researchers conducted this phase 3 trial, RTOG 0522 (NCT00265941), to determine if adding cetuximab to radiotherapy and cisplatin would improve progression-free survival.

The trial included 891 evaluable patients with stage T2 N2a-3 M0 or T3-4 N0-3 M0 disease. They were randomized to receive radiotherapy and cisplatin without cetuximab (n = 447) or with cetuximab (n = 444). Most patients were assigned to intensity-modulated radiotherapy (86.8% in the radiotherapy/cisplatin arm and 89.2% in the cetuximab arm) rather than 3-D conformal radiotherapy (13.2% and 10.8%, respectively).

Baseline characteristics were balanced between the treatment arms. The median age was 57 years (range, 31-79 years) in the radiotherapy/cisplatin arm and 58 years (range, 34-76 years) in the cetuximab arm. Nearly 90% of patients in both arms were men, and the oropharynx was the primary site of disease in about 70% of patients in both arms.

More patients were p16-positive (35.7% in the radiotherapy/cisplatin arm and 39.4% in the cetuximab arm) than were p16-negative (14.4% and 13.1%, respectively). However, p16 status was unknown for about half of patients in each arm.
 

Long-term efficacy

At a median follow-up of 10.1 years, 452 patients were still alive.

The rate of local-regional failure was 28.5% in the radiotherapy/cisplatin arm and 34.8% in the cetuximab arm (hazard ratio, 1.21; P = .94). The rate of distant metastases was 15% and 11.8%, respectively (HR, 0.79; P = .10).

The 10-year progression-free survival rate was 43.6% in the radiotherapy/cisplatin arm and 40.2% in the cetuximab arm (HR, 1.06; P = .74). The 10-year overall survival rate was 49.9% and 50%, respectively (HR, 0.97; P = .36)

“As might be expected, patients who were p16-positive had a substantially improved progression-free survival as well as overall survival,” Dr. Caudell said. “Patients who had p16-negative oropharyngeal cancer or nonoropharyngeal cancer had equivalent progression-free survival and overall survival.”

However, the addition of cetuximab did not improve progression-free or overall survival in patients with p16-positive, p16-negative oropharyngeal, or nonoropharyngeal cancers.

“[These results] have proven conclusively that the addition of cetuximab to concurrent cisplatin and radiation therapy does not improve outcomes in stage III-IV head and neck cancer, regardless of the primary tumor site and p16 status,” said Kartik Sehgal, MD, of Beth Israel Deaconess Medical Center in Boston, who was not involved in this study.
 

Late toxicity

Dr. Caudell noted that late toxicity was “substantial” in both treatment arms. Late toxicity was defined as adverse events occurring greater than 90 days from the start of radiotherapy.

The incidence of grade 3/4 late toxicity was 57.4% in the radiotherapy/cisplatin arm and 61.3% in the cetuximab arm (P = .26). The most common grade 3/4 late adverse event was dysphagia, occurring in 39.6% of patients in the radiotherapy/cisplatin arm and 38.2% of those in the cetuximab arm.

Other late grade 3/4 events (in the radiotherapy/cisplatin and cetuximab arms, respectively) included dry mouth (3% and 5%), radiation mucositis (5.3% and 7%), weight decrease (7.6% and 8.7%), hearing impairment (6% and 5%), pharynx mucositis/stomatitis (4.9% and 6%), and osteonecrosis (6% and 4.8%).

Feeding tube use was similar in both treatment arms over time. At 10 years, 14.3% of patients in the radiotherapy/cisplatin arm and 11% of those in the cetuximab arm used a feeding tube (P = .53).

“Despite the use of intensity-modulated radiotherapy, there was a high incidence of late grade 3 and higher toxicities, primarily related to dysphagia, which have substantial effects on the quality of life of our patients,” Dr. Sehgal noted. “These findings need to be considered carefully while designing future studies.

“Future directions for the management of locoregionally advanced head and neck cancer include evaluation of benefits from the addition of immune checkpoint inhibitors to cisplatin with concurrent radiation therapy (e.g., JAVELIN with avelumab [NCT01772004], KEYNOTE-412 with pembrolizumab [NCT03040999], and NCT03349710 with nivolumab) and whether immune checkpoint inhibitors can substitute for cisplatin in those being treated concurrently with radiation therapy (e.g., REACH trial comparing avelumab, cetuximab, and radiation therapy versus cisplatin plus radiation therapy [NCT02999087]).”

The current study was sponsored by the Radiation Therapy Oncology Group, the National Cancer Institute, NRG Oncology, and Eli Lilly. Dr. Caudell disclosed grants and fees from Varian Medical Systems. Dr. Sehgal had no conflicts of interest to disclose.

jensmith@mdedge.com

SOURCE: Caudell J et al. Head and Neck Cancers Symposium 2020, Abstract 6.

Adding cetuximab to radiotherapy and cisplatin does not improve outcomes in patients with locoregionally advanced head and neck carcinoma, according to 10-year follow-up from a phase 3 trial.

The addition of cetuximab did not reduce local-regional failure or distant metastasis, and it did not improve progression-free or overall survival.

“With a median follow-up of over 10 years, this updated report confirms the addition of cetuximab to radiation/cisplatin did not improve any measured outcome in the entire cohort or when stratifying by p16 status,” said Jimmy J. Caudell, MD, of Moffitt Cancer Center in Tampa, Fla.

Dr. Caudell presented this update at the Multidisciplinary Head and Neck Cancer Symposium, sponsored by the American Society for Radiation Oncology.

Dr. Caudell noted that cisplatin plus radiotherapy or cetuximab plus radiotherapy have been shown to improve overall survival in patients with locoregionally advanced head and neck carcinoma. Researchers conducted this phase 3 trial, RTOG 0522 (NCT00265941), to determine if adding cetuximab to radiotherapy and cisplatin would improve progression-free survival.

The trial included 891 evaluable patients with stage T2 N2a-3 M0 or T3-4 N0-3 M0 disease. They were randomized to receive radiotherapy and cisplatin without cetuximab (n = 447) or with cetuximab (n = 444). Most patients were assigned to intensity-modulated radiotherapy (86.8% in the radiotherapy/cisplatin arm and 89.2% in the cetuximab arm) rather than 3-D conformal radiotherapy (13.2% and 10.8%, respectively).

Baseline characteristics were balanced between the treatment arms. The median age was 57 years (range, 31-79 years) in the radiotherapy/cisplatin arm and 58 years (range, 34-76 years) in the cetuximab arm. Nearly 90% of patients in both arms were men, and the oropharynx was the primary site of disease in about 70% of patients in both arms.

More patients were p16-positive (35.7% in the radiotherapy/cisplatin arm and 39.4% in the cetuximab arm) than were p16-negative (14.4% and 13.1%, respectively). However, p16 status was unknown for about half of patients in each arm.
 

Long-term efficacy

At a median follow-up of 10.1 years, 452 patients were still alive.

The rate of local-regional failure was 28.5% in the radiotherapy/cisplatin arm and 34.8% in the cetuximab arm (hazard ratio, 1.21; P = .94). The rate of distant metastases was 15% and 11.8%, respectively (HR, 0.79; P = .10).

The 10-year progression-free survival rate was 43.6% in the radiotherapy/cisplatin arm and 40.2% in the cetuximab arm (HR, 1.06; P = .74). The 10-year overall survival rate was 49.9% and 50%, respectively (HR, 0.97; P = .36)

“As might be expected, patients who were p16-positive had a substantially improved progression-free survival as well as overall survival,” Dr. Caudell said. “Patients who had p16-negative oropharyngeal cancer or nonoropharyngeal cancer had equivalent progression-free survival and overall survival.”

However, the addition of cetuximab did not improve progression-free or overall survival in patients with p16-positive, p16-negative oropharyngeal, or nonoropharyngeal cancers.

“[These results] have proven conclusively that the addition of cetuximab to concurrent cisplatin and radiation therapy does not improve outcomes in stage III-IV head and neck cancer, regardless of the primary tumor site and p16 status,” said Kartik Sehgal, MD, of Beth Israel Deaconess Medical Center in Boston, who was not involved in this study.
 

Late toxicity

Dr. Caudell noted that late toxicity was “substantial” in both treatment arms. Late toxicity was defined as adverse events occurring greater than 90 days from the start of radiotherapy.

The incidence of grade 3/4 late toxicity was 57.4% in the radiotherapy/cisplatin arm and 61.3% in the cetuximab arm (P = .26). The most common grade 3/4 late adverse event was dysphagia, occurring in 39.6% of patients in the radiotherapy/cisplatin arm and 38.2% of those in the cetuximab arm.

Other late grade 3/4 events (in the radiotherapy/cisplatin and cetuximab arms, respectively) included dry mouth (3% and 5%), radiation mucositis (5.3% and 7%), weight decrease (7.6% and 8.7%), hearing impairment (6% and 5%), pharynx mucositis/stomatitis (4.9% and 6%), and osteonecrosis (6% and 4.8%).

Feeding tube use was similar in both treatment arms over time. At 10 years, 14.3% of patients in the radiotherapy/cisplatin arm and 11% of those in the cetuximab arm used a feeding tube (P = .53).

“Despite the use of intensity-modulated radiotherapy, there was a high incidence of late grade 3 and higher toxicities, primarily related to dysphagia, which have substantial effects on the quality of life of our patients,” Dr. Sehgal noted. “These findings need to be considered carefully while designing future studies.

“Future directions for the management of locoregionally advanced head and neck cancer include evaluation of benefits from the addition of immune checkpoint inhibitors to cisplatin with concurrent radiation therapy (e.g., JAVELIN with avelumab [NCT01772004], KEYNOTE-412 with pembrolizumab [NCT03040999], and NCT03349710 with nivolumab) and whether immune checkpoint inhibitors can substitute for cisplatin in those being treated concurrently with radiation therapy (e.g., REACH trial comparing avelumab, cetuximab, and radiation therapy versus cisplatin plus radiation therapy [NCT02999087]).”

The current study was sponsored by the Radiation Therapy Oncology Group, the National Cancer Institute, NRG Oncology, and Eli Lilly. Dr. Caudell disclosed grants and fees from Varian Medical Systems. Dr. Sehgal had no conflicts of interest to disclose.

jensmith@mdedge.com

SOURCE: Caudell J et al. Head and Neck Cancers Symposium 2020, Abstract 6.

Preoperative nivolumab, with or without ipilimumab, appeared safe and effective in a phase 2 trial of patients with oral cavity squamous cell carcinoma (OCSCC).

“We found that nivolumab, with or without ipilimumab, was feasible prior to surgery in patients with oral cavity cancers, with no delays in surgery observed,” said Jonathan D. Schoenfeld, MD, of the Dana-Farber/Brigham and Women’s Cancer Center in Boston.

“We did observe promising rates of volumetric and pathologic response, with near-complete and complete responses observed, particularly in the nivo-ipi arm.”

Dr. Schoenfeld presented these results at the Multidisciplinary Head and Neck Cancer Symposium, sponsored by the American Society for Radiation Oncology.

“The rationale behind evaluation of neoadjuvant immunotherapy is the potential of tumor downstaging, converting unresectable disease to resectable and inducing durable immunological memory as a result of exposure to the full breadth of tumor antigens preoperatively,” said Kartik Sehgal, MD, of Beth Israel Deaconess Medical Center in Boston, who was not involved in this study.

“This randomized, phase 2 window study ... found that treatment with two neoadjuvant cycles of nivolumab alone or along with ipilimumab during the first cycle was feasible from an adverse events perspective and led to volumetric responses in approximately 50% of patients.”
 

Patients and treatment

The trial (NCT02919683) enrolled 30 patients with OCSCC, but 1 patient was excluded due to metastases at baseline. Patients had T2 (n = 20) or greater (n = 9) disease at baseline, and 58% of patients (n = 17) had node-positive disease.

The patients were randomized to two cycles of nivolumab (3 mg/kg) or nivolumab (3 mg/kg) plus ipilimumab (1 mg/kg with the first cycle). Patients underwent surgery 3-7 days after completing cycle 2.

In the nivolumab monotherapy arm (n = 14), the median age was 64.4 years (range, 39.1-81 years), and 71.4% of patients were men. Oral tongue was the primary tumor site in 50% of patients, and 50% of patients had stage IV disease.

In the nivolumab-ipilimumab arm (n = 15), the median age was 65.2 years (range, 32.5-78.4 years), and 53.3% of patients were men. Oral tongue was the primary tumor site in 60% of patients, and 73.3% of patients had stage IV disease.
 

Safety and tolerability

Six patients did not receive the full cycle 2 dose of immunotherapy, two in the nivolumab arm and four in the nivolumab-ipilimumab arm. This was most commonly due to an infusion reaction during cycle 2, Dr. Schoenfeld said.

There were no cases in which surgery was delayed. However, one patient did have surgery moved to an earlier date after cycle 1 because of concerns about progression.

There were three severe immune-related adverse events. In the nivolumab-ipilimumab arm, there was a case of grade 3 pneumonitis and a case of grade 3 colitis. Both of these events were reversible with treatment.

In the nivolumab monotherapy arm, one patient had grade 4 new-onset diabetes with diabetic ketoacidosis. This patient is still insulin dependent.

Perioperative adverse events in both arms included pulmonary embolism, postoperative hematoma, and flap failures (n = 2). One patient with flap failure also had a perioperative stroke, experienced progressive clinical decline, and ultimately died.
 

Response and survival

In the nivolumab monotherapy arm, 50% of patients (n = 7) had a volumetric response, and 8% (n = 1) had a pathologic complete response.

In the nivolumab-ipilimumab arm, 53% of patients (n = 8) had a volumetric response, and 20% (n = 3) had a pathologic complete response.

“In general, we found that our response metrics were concordant; that is, patients with volumetric responses tended more frequently to have pathologic responses,” Dr. Schoenfeld said. “There were a couple notable cases where there were volumetric increases and significant pathologic responses.”

To identify factors associated with response, Dr. Schoenfeld and colleagues performed correlative multiplex immunofluorescence on 21 patient specimens prior to treatment.

“We did not identify any differences in baseline levels of PD-L1 expression in tumor cells between the two arms,” Dr. Schoenfeld noted. “We found that CD4-positive T cells in the pretreatment specimens correlated with pathologic response [P = .016]. Interestingly, this association was only significant in patients treated with nivo-ipi [P = .008] but not nivolumab alone [P = .83].”

Ten patients went on to receive radiation, and nine received chemoradiation. One patient presented to the operating room but did not undergo surgery because he was thought to require total glossectomy. This patient received chemoradiotherapy, achieved a complete response, and is still disease free after more than 3 years of follow-up.

The median follow-up for the entire cohort was 14 months. At 12 months, the progression-free survival rate was 85%, and the overall survival rate was 89%.

Dr. Schoenfeld noted that this study was not powered to assess survival or to directly compare nivolumab monotherapy and nivolumab plus ipilimumab.
 

‘Encouraging’ results, but what’s next?

“We were very encouraged by the toxicity data ... [and] the impressive pathologic responses in both arms, but particularly in the nivo-ipi arm,” Dr. Schoenfeld said. “I think the real question is, ‘Does this translate into a significant progression-free or overall survival advantage?’ So I think that would be something worthy of further study.”

“These results are encouraging for management of patients with oral cavity cancers who remain at high risk for recurrence with the current standard of care but will need validation in larger prospective studies,” Dr. Sehgal noted. “Multiple clinical trials are currently ongoing to evaluate the role of neoadjuvant immunotherapy for disease-specific outcomes, notable being phase 2 NCT02296684 and phase 3 KEYNOTE-689 (NCT03765918) with pembrolizumab and phase 3 IMSTAR-HN (NCT03700905) with nivolumab alone or along with ipilimumab.”

The current study was funded by Bristol-Myers Squibb. Dr. Schoenfeld disclosed relationships with Bristol-Myers Squibb and other companies. Dr. Sehgal had no relevant conflicts to disclose.

jensmith@mdedge.com

SOURCE: Schoenfeld J et al. Head and Neck Cancers Symposium 2020, Abstract 1.

Preoperative nivolumab, with or without ipilimumab, appeared safe and effective in a phase 2 trial of patients with oral cavity squamous cell carcinoma (OCSCC).

“We found that nivolumab, with or without ipilimumab, was feasible prior to surgery in patients with oral cavity cancers, with no delays in surgery observed,” said Jonathan D. Schoenfeld, MD, of the Dana-Farber/Brigham and Women’s Cancer Center in Boston.

“We did observe promising rates of volumetric and pathologic response, with near-complete and complete responses observed, particularly in the nivo-ipi arm.”

Dr. Schoenfeld presented these results at the Multidisciplinary Head and Neck Cancer Symposium, sponsored by the American Society for Radiation Oncology.

“The rationale behind evaluation of neoadjuvant immunotherapy is the potential of tumor downstaging, converting unresectable disease to resectable and inducing durable immunological memory as a result of exposure to the full breadth of tumor antigens preoperatively,” said Kartik Sehgal, MD, of Beth Israel Deaconess Medical Center in Boston, who was not involved in this study.

“This randomized, phase 2 window study ... found that treatment with two neoadjuvant cycles of nivolumab alone or along with ipilimumab during the first cycle was feasible from an adverse events perspective and led to volumetric responses in approximately 50% of patients.”
 

Patients and treatment

The trial (NCT02919683) enrolled 30 patients with OCSCC, but 1 patient was excluded due to metastases at baseline. Patients had T2 (n = 20) or greater (n = 9) disease at baseline, and 58% of patients (n = 17) had node-positive disease.

The patients were randomized to two cycles of nivolumab (3 mg/kg) or nivolumab (3 mg/kg) plus ipilimumab (1 mg/kg with the first cycle). Patients underwent surgery 3-7 days after completing cycle 2.

In the nivolumab monotherapy arm (n = 14), the median age was 64.4 years (range, 39.1-81 years), and 71.4% of patients were men. Oral tongue was the primary tumor site in 50% of patients, and 50% of patients had stage IV disease.

In the nivolumab-ipilimumab arm (n = 15), the median age was 65.2 years (range, 32.5-78.4 years), and 53.3% of patients were men. Oral tongue was the primary tumor site in 60% of patients, and 73.3% of patients had stage IV disease.
 

Safety and tolerability

Six patients did not receive the full cycle 2 dose of immunotherapy, two in the nivolumab arm and four in the nivolumab-ipilimumab arm. This was most commonly due to an infusion reaction during cycle 2, Dr. Schoenfeld said.

There were no cases in which surgery was delayed. However, one patient did have surgery moved to an earlier date after cycle 1 because of concerns about progression.

There were three severe immune-related adverse events. In the nivolumab-ipilimumab arm, there was a case of grade 3 pneumonitis and a case of grade 3 colitis. Both of these events were reversible with treatment.

In the nivolumab monotherapy arm, one patient had grade 4 new-onset diabetes with diabetic ketoacidosis. This patient is still insulin dependent.

Perioperative adverse events in both arms included pulmonary embolism, postoperative hematoma, and flap failures (n = 2). One patient with flap failure also had a perioperative stroke, experienced progressive clinical decline, and ultimately died.
 

Response and survival

In the nivolumab monotherapy arm, 50% of patients (n = 7) had a volumetric response, and 8% (n = 1) had a pathologic complete response.

In the nivolumab-ipilimumab arm, 53% of patients (n = 8) had a volumetric response, and 20% (n = 3) had a pathologic complete response.

“In general, we found that our response metrics were concordant; that is, patients with volumetric responses tended more frequently to have pathologic responses,” Dr. Schoenfeld said. “There were a couple notable cases where there were volumetric increases and significant pathologic responses.”

To identify factors associated with response, Dr. Schoenfeld and colleagues performed correlative multiplex immunofluorescence on 21 patient specimens prior to treatment.

“We did not identify any differences in baseline levels of PD-L1 expression in tumor cells between the two arms,” Dr. Schoenfeld noted. “We found that CD4-positive T cells in the pretreatment specimens correlated with pathologic response [P = .016]. Interestingly, this association was only significant in patients treated with nivo-ipi [P = .008] but not nivolumab alone [P = .83].”

Ten patients went on to receive radiation, and nine received chemoradiation. One patient presented to the operating room but did not undergo surgery because he was thought to require total glossectomy. This patient received chemoradiotherapy, achieved a complete response, and is still disease free after more than 3 years of follow-up.

The median follow-up for the entire cohort was 14 months. At 12 months, the progression-free survival rate was 85%, and the overall survival rate was 89%.

Dr. Schoenfeld noted that this study was not powered to assess survival or to directly compare nivolumab monotherapy and nivolumab plus ipilimumab.
 

‘Encouraging’ results, but what’s next?

“We were very encouraged by the toxicity data ... [and] the impressive pathologic responses in both arms, but particularly in the nivo-ipi arm,” Dr. Schoenfeld said. “I think the real question is, ‘Does this translate into a significant progression-free or overall survival advantage?’ So I think that would be something worthy of further study.”

“These results are encouraging for management of patients with oral cavity cancers who remain at high risk for recurrence with the current standard of care but will need validation in larger prospective studies,” Dr. Sehgal noted. “Multiple clinical trials are currently ongoing to evaluate the role of neoadjuvant immunotherapy for disease-specific outcomes, notable being phase 2 NCT02296684 and phase 3 KEYNOTE-689 (NCT03765918) with pembrolizumab and phase 3 IMSTAR-HN (NCT03700905) with nivolumab alone or along with ipilimumab.”

The current study was funded by Bristol-Myers Squibb. Dr. Schoenfeld disclosed relationships with Bristol-Myers Squibb and other companies. Dr. Sehgal had no relevant conflicts to disclose.

jensmith@mdedge.com

SOURCE: Schoenfeld J et al. Head and Neck Cancers Symposium 2020, Abstract 1.

Preoperative nivolumab, with or without ipilimumab, appeared safe and effective in a phase 2 trial of patients with oral cavity squamous cell carcinoma (OCSCC).

“We found that nivolumab, with or without ipilimumab, was feasible prior to surgery in patients with oral cavity cancers, with no delays in surgery observed,” said Jonathan D. Schoenfeld, MD, of the Dana-Farber/Brigham and Women’s Cancer Center in Boston.

“We did observe promising rates of volumetric and pathologic response, with near-complete and complete responses observed, particularly in the nivo-ipi arm.”

Dr. Schoenfeld presented these results at the Multidisciplinary Head and Neck Cancer Symposium, sponsored by the American Society for Radiation Oncology.

“The rationale behind evaluation of neoadjuvant immunotherapy is the potential of tumor downstaging, converting unresectable disease to resectable and inducing durable immunological memory as a result of exposure to the full breadth of tumor antigens preoperatively,” said Kartik Sehgal, MD, of Beth Israel Deaconess Medical Center in Boston, who was not involved in this study.

“This randomized, phase 2 window study ... found that treatment with two neoadjuvant cycles of nivolumab alone or along with ipilimumab during the first cycle was feasible from an adverse events perspective and led to volumetric responses in approximately 50% of patients.”
 

Patients and treatment

The trial (NCT02919683) enrolled 30 patients with OCSCC, but 1 patient was excluded due to metastases at baseline. Patients had T2 (n = 20) or greater (n = 9) disease at baseline, and 58% of patients (n = 17) had node-positive disease.

The patients were randomized to two cycles of nivolumab (3 mg/kg) or nivolumab (3 mg/kg) plus ipilimumab (1 mg/kg with the first cycle). Patients underwent surgery 3-7 days after completing cycle 2.

In the nivolumab monotherapy arm (n = 14), the median age was 64.4 years (range, 39.1-81 years), and 71.4% of patients were men. Oral tongue was the primary tumor site in 50% of patients, and 50% of patients had stage IV disease.

In the nivolumab-ipilimumab arm (n = 15), the median age was 65.2 years (range, 32.5-78.4 years), and 53.3% of patients were men. Oral tongue was the primary tumor site in 60% of patients, and 73.3% of patients had stage IV disease.
 

Safety and tolerability

Six patients did not receive the full cycle 2 dose of immunotherapy, two in the nivolumab arm and four in the nivolumab-ipilimumab arm. This was most commonly due to an infusion reaction during cycle 2, Dr. Schoenfeld said.

There were no cases in which surgery was delayed. However, one patient did have surgery moved to an earlier date after cycle 1 because of concerns about progression.

There were three severe immune-related adverse events. In the nivolumab-ipilimumab arm, there was a case of grade 3 pneumonitis and a case of grade 3 colitis. Both of these events were reversible with treatment.

In the nivolumab monotherapy arm, one patient had grade 4 new-onset diabetes with diabetic ketoacidosis. This patient is still insulin dependent.

Perioperative adverse events in both arms included pulmonary embolism, postoperative hematoma, and flap failures (n = 2). One patient with flap failure also had a perioperative stroke, experienced progressive clinical decline, and ultimately died.
 

Response and survival

In the nivolumab monotherapy arm, 50% of patients (n = 7) had a volumetric response, and 8% (n = 1) had a pathologic complete response.

In the nivolumab-ipilimumab arm, 53% of patients (n = 8) had a volumetric response, and 20% (n = 3) had a pathologic complete response.

“In general, we found that our response metrics were concordant; that is, patients with volumetric responses tended more frequently to have pathologic responses,” Dr. Schoenfeld said. “There were a couple notable cases where there were volumetric increases and significant pathologic responses.”

To identify factors associated with response, Dr. Schoenfeld and colleagues performed correlative multiplex immunofluorescence on 21 patient specimens prior to treatment.

“We did not identify any differences in baseline levels of PD-L1 expression in tumor cells between the two arms,” Dr. Schoenfeld noted. “We found that CD4-positive T cells in the pretreatment specimens correlated with pathologic response [P = .016]. Interestingly, this association was only significant in patients treated with nivo-ipi [P = .008] but not nivolumab alone [P = .83].”

Ten patients went on to receive radiation, and nine received chemoradiation. One patient presented to the operating room but did not undergo surgery because he was thought to require total glossectomy. This patient received chemoradiotherapy, achieved a complete response, and is still disease free after more than 3 years of follow-up.

The median follow-up for the entire cohort was 14 months. At 12 months, the progression-free survival rate was 85%, and the overall survival rate was 89%.

Dr. Schoenfeld noted that this study was not powered to assess survival or to directly compare nivolumab monotherapy and nivolumab plus ipilimumab.
 

‘Encouraging’ results, but what’s next?

“We were very encouraged by the toxicity data ... [and] the impressive pathologic responses in both arms, but particularly in the nivo-ipi arm,” Dr. Schoenfeld said. “I think the real question is, ‘Does this translate into a significant progression-free or overall survival advantage?’ So I think that would be something worthy of further study.”

“These results are encouraging for management of patients with oral cavity cancers who remain at high risk for recurrence with the current standard of care but will need validation in larger prospective studies,” Dr. Sehgal noted. “Multiple clinical trials are currently ongoing to evaluate the role of neoadjuvant immunotherapy for disease-specific outcomes, notable being phase 2 NCT02296684 and phase 3 KEYNOTE-689 (NCT03765918) with pembrolizumab and phase 3 IMSTAR-HN (NCT03700905) with nivolumab alone or along with ipilimumab.”

The current study was funded by Bristol-Myers Squibb. Dr. Schoenfeld disclosed relationships with Bristol-Myers Squibb and other companies. Dr. Sehgal had no relevant conflicts to disclose.

jensmith@mdedge.com

SOURCE: Schoenfeld J et al. Head and Neck Cancers Symposium 2020, Abstract 1.

The Food and Drug Administration has approved neratinib (NERLYNX) in combination with capecitabine for use in adults with advanced or metastatic HER2-positive breast cancer who have received at least two prior anti-HER2 based regimens in the metastatic setting.

The recommended dose for neratinib in this population is 240 mg once daily with food on days 1-21 of a 21-day cycle. Neratinib should be given with capecitabine at 750 mg/m² twice daily on days 1-14 until progression or unacceptable toxicity.

The full prescribing information for neratinib is available from the FDA website.

The FDA’s new approval of neratinib is based on results from the NALA trial (NCT01808573). The trial enrolled 621 patients with metastatic HER2-positive breast cancer who had received at least two prior anti-HER2 based regimens in the metastatic setting.

The patients were randomized to neratinib plus capecitabine or lapatinib plus capecitabine and received treatment until progression or unacceptable toxicity.

The objective response rate was 32.8% in the neratinib arm and 26.7% in the lapatinib arm. The median duration of response was 8.5 months and 5.6 months, respectively.

The median progression-free survival was 5.6 months in the neratinib arm and 5.5 months in the lapatinib arm (hazard ratio 0.76; P = .0059). The median overall survival was 21 months and 18.7 months, respectively (HR 0.88; P = .2086).

The most common grade 3/4 adverse events in the neratinib arm were diarrhea, nausea, vomiting, fatigue, and decreased appetite.

jensmith@mdedge.com

The Food and Drug Administration has approved neratinib (NERLYNX) in combination with capecitabine for use in adults with advanced or metastatic HER2-positive breast cancer who have received at least two prior anti-HER2 based regimens in the metastatic setting.

The recommended dose for neratinib in this population is 240 mg once daily with food on days 1-21 of a 21-day cycle. Neratinib should be given with capecitabine at 750 mg/m² twice daily on days 1-14 until progression or unacceptable toxicity.

The full prescribing information for neratinib is available from the FDA website.

The FDA’s new approval of neratinib is based on results from the NALA trial (NCT01808573). The trial enrolled 621 patients with metastatic HER2-positive breast cancer who had received at least two prior anti-HER2 based regimens in the metastatic setting.

The patients were randomized to neratinib plus capecitabine or lapatinib plus capecitabine and received treatment until progression or unacceptable toxicity.

The objective response rate was 32.8% in the neratinib arm and 26.7% in the lapatinib arm. The median duration of response was 8.5 months and 5.6 months, respectively.

The median progression-free survival was 5.6 months in the neratinib arm and 5.5 months in the lapatinib arm (hazard ratio 0.76; P = .0059). The median overall survival was 21 months and 18.7 months, respectively (HR 0.88; P = .2086).

The most common grade 3/4 adverse events in the neratinib arm were diarrhea, nausea, vomiting, fatigue, and decreased appetite.

jensmith@mdedge.com

The Food and Drug Administration has approved neratinib (NERLYNX) in combination with capecitabine for use in adults with advanced or metastatic HER2-positive breast cancer who have received at least two prior anti-HER2 based regimens in the metastatic setting.

The recommended dose for neratinib in this population is 240 mg once daily with food on days 1-21 of a 21-day cycle. Neratinib should be given with capecitabine at 750 mg/m² twice daily on days 1-14 until progression or unacceptable toxicity.

The full prescribing information for neratinib is available from the FDA website.

The FDA’s new approval of neratinib is based on results from the NALA trial (NCT01808573). The trial enrolled 621 patients with metastatic HER2-positive breast cancer who had received at least two prior anti-HER2 based regimens in the metastatic setting.

The patients were randomized to neratinib plus capecitabine or lapatinib plus capecitabine and received treatment until progression or unacceptable toxicity.

The objective response rate was 32.8% in the neratinib arm and 26.7% in the lapatinib arm. The median duration of response was 8.5 months and 5.6 months, respectively.

The median progression-free survival was 5.6 months in the neratinib arm and 5.5 months in the lapatinib arm (hazard ratio 0.76; P = .0059). The median overall survival was 21 months and 18.7 months, respectively (HR 0.88; P = .2086).

The most common grade 3/4 adverse events in the neratinib arm were diarrhea, nausea, vomiting, fatigue, and decreased appetite.

jensmith@mdedge.com

First-in-human results suggest a gene therapy, BAY 2599023, can increase factor VIII levels in patients with hemophilia A, but it isn’t clear if BAY 2599023 can eliminate the need for prophylaxis.

©designer491/Thinkstock

Of four patients who received BAY 2599023, three achieved clinically meaningful factor VIII levels, and all were able to stop prophylaxis at some point. However, one patient had to resume prophylaxis, and all four have experienced bleeds since receiving BAY 2599023.

This is a dose-escalating trial (NCT03588299), so researchers are still attempting to determine the optimal dose of BAY 2599023. Upcoming results in two patients treated at the highest dose should provide more insight, according to Steven W. Pipe, MD, of the University of Michigan in Ann Arbor.

Dr. Pipe presented results with BAY 2599023 at the annual congress of the European Association for Haemophilia and Allied Disorders.

He noted that between 30% and 70% of hemophilia patients may have preexisting neutralizing antibodies to specific adeno-associated virus (AAV) serotypes. Developing gene therapies with varying serotypes could reduce this problem and increase eligibility for gene therapy. Bayer had this in mind when developing BAY 2599023.

BAY 2599023 is a non-replicating AAV vector, based on the AAV serotype hu37, which contains a single-stranded DNA genome encoding a B-domain deleted factor VIII, under the control of a liver-specific promotor/enhancer combination optimized for transgenic expression, Dr. Pipe explained.

He presented results with BAY 2599023 in four patients with severe hemophilia A. At baseline, patients were receiving prophylaxis and did not have factor VIII inhibitors or detectable immunity to the AAVhu37 capsid.
 

First cohort

Two patients received BAY 2599023 at a dose of 0.5 × 10¹³ GC/kg. One patient achieved a factor VIII level above 5% at this dose and was able to stop prophylaxis temporarily. The patient experienced two bleeds on study and had to resume prophylaxis because of a target joint.

“He came into the study with a particularly challenging target joint in his ankle, and he had known from experience on prophylaxis that, if his factor level got too low, he would have breakthrough bleeds,” Dr. Pipe explained. “So we agreed that if he didn’t achieve a sustained level above 5%, he would go back on prophylaxis. He was able to stay off prophylaxis for 6 weeks, but we had to put him back on because of breakthrough bleeding.”

Dr. Pipe and colleagues have been following this patient for about a year, and the patient still has factor VIII levels of about 2% to 3% after a washout of prophylaxis.

The other patient who received a dose of 0.5 × 10¹³ GC/kg came off prophylaxis early on and has sustained factor VIII levels of 20%. This patient had four bleeds early in the trial but has since done very well, Dr. Pipe said. The patient had 99 bleeds in the year prior to receiving BAY 2599023.
 

Second cohort

Two subsequent patients received BAY 2599023 at a dose of 1 × 10¹³ GC/kg. Both patients have stopped prophylaxis.

One patient achieved factor VIII levels in the 5%-10% range and stopped prophylaxis at day 49. The patient has received on-demand treatment for four bleeds. The other patient achieved “robust” factor VIII expression levels “well above 20%,” according to Dr. Pipe. This patient stopped prophylaxis at day 10 and experienced bleeds early on but has remained bleed-free and treatment-free for 7 months.

Dr. Pipe noted that this patient experienced a spike in transaminases “very early on” after receiving BAY 2599023.

“So he was put on prednisone, but his liver enzymes almost immediately corrected to within the normal range,” Dr. Pipe said. “He has finished the cascading dose of prednisone, his liver enzymes have remained stable, his factor VIII expression has remained stable, and he continues to do very well.”
 

Next steps

Based on results in the first two cohorts, researchers are proceeding with a higher dose of BAY 2599023.

“The overall goal of this study is to identify the optimal dose that can be taken forward to the planned phase 3 study,” Dr. Pipe said. “What they [Bayer] would like to bring to the community is a product that offers a chance for maximum eligibility based on low screen out because of preexisting immunity and maximize the number of patients who are in the normal range.”

“For patients to embrace gene therapy, it really has to get them at least the possibility to land within the normal range and, hopefully, be not just liberated from prophylaxis but maybe liberated from the need for factor VIII at all,” Dr. Pipe added. “I think if these AAV platform therapies can’t deliver that on a relatively consistent basis, it’s going to be challenging to get patients to embrace this technology.”

The phase 1/2 trial is sponsored by Bayer in collaboration with Ultragenyx Pharmaceutical Inc. Dr. Pipe disclosed relationships with Bayer and other companies.

jensmith@mdedge.com

SOURCE: Pipe SW et al. EAHAD 2020. Abstract P190.

First-in-human results suggest a gene therapy, BAY 2599023, can increase factor VIII levels in patients with hemophilia A, but it isn’t clear if BAY 2599023 can eliminate the need for prophylaxis.

©designer491/Thinkstock

Of four patients who received BAY 2599023, three achieved clinically meaningful factor VIII levels, and all were able to stop prophylaxis at some point. However, one patient had to resume prophylaxis, and all four have experienced bleeds since receiving BAY 2599023.

This is a dose-escalating trial (NCT03588299), so researchers are still attempting to determine the optimal dose of BAY 2599023. Upcoming results in two patients treated at the highest dose should provide more insight, according to Steven W. Pipe, MD, of the University of Michigan in Ann Arbor.

Dr. Pipe presented results with BAY 2599023 at the annual congress of the European Association for Haemophilia and Allied Disorders.

He noted that between 30% and 70% of hemophilia patients may have preexisting neutralizing antibodies to specific adeno-associated virus (AAV) serotypes. Developing gene therapies with varying serotypes could reduce this problem and increase eligibility for gene therapy. Bayer had this in mind when developing BAY 2599023.

BAY 2599023 is a non-replicating AAV vector, based on the AAV serotype hu37, which contains a single-stranded DNA genome encoding a B-domain deleted factor VIII, under the control of a liver-specific promotor/enhancer combination optimized for transgenic expression, Dr. Pipe explained.

He presented results with BAY 2599023 in four patients with severe hemophilia A. At baseline, patients were receiving prophylaxis and did not have factor VIII inhibitors or detectable immunity to the AAVhu37 capsid.
 

First cohort

Two patients received BAY 2599023 at a dose of 0.5 × 10¹³ GC/kg. One patient achieved a factor VIII level above 5% at this dose and was able to stop prophylaxis temporarily. The patient experienced two bleeds on study and had to resume prophylaxis because of a target joint.

“He came into the study with a particularly challenging target joint in his ankle, and he had known from experience on prophylaxis that, if his factor level got too low, he would have breakthrough bleeds,” Dr. Pipe explained. “So we agreed that if he didn’t achieve a sustained level above 5%, he would go back on prophylaxis. He was able to stay off prophylaxis for 6 weeks, but we had to put him back on because of breakthrough bleeding.”

Dr. Pipe and colleagues have been following this patient for about a year, and the patient still has factor VIII levels of about 2% to 3% after a washout of prophylaxis.

The other patient who received a dose of 0.5 × 10¹³ GC/kg came off prophylaxis early on and has sustained factor VIII levels of 20%. This patient had four bleeds early in the trial but has since done very well, Dr. Pipe said. The patient had 99 bleeds in the year prior to receiving BAY 2599023.
 

Second cohort

Two subsequent patients received BAY 2599023 at a dose of 1 × 10¹³ GC/kg. Both patients have stopped prophylaxis.

One patient achieved factor VIII levels in the 5%-10% range and stopped prophylaxis at day 49. The patient has received on-demand treatment for four bleeds. The other patient achieved “robust” factor VIII expression levels “well above 20%,” according to Dr. Pipe. This patient stopped prophylaxis at day 10 and experienced bleeds early on but has remained bleed-free and treatment-free for 7 months.

Dr. Pipe noted that this patient experienced a spike in transaminases “very early on” after receiving BAY 2599023.

“So he was put on prednisone, but his liver enzymes almost immediately corrected to within the normal range,” Dr. Pipe said. “He has finished the cascading dose of prednisone, his liver enzymes have remained stable, his factor VIII expression has remained stable, and he continues to do very well.”
 

Next steps

Based on results in the first two cohorts, researchers are proceeding with a higher dose of BAY 2599023.

“The overall goal of this study is to identify the optimal dose that can be taken forward to the planned phase 3 study,” Dr. Pipe said. “What they [Bayer] would like to bring to the community is a product that offers a chance for maximum eligibility based on low screen out because of preexisting immunity and maximize the number of patients who are in the normal range.”

“For patients to embrace gene therapy, it really has to get them at least the possibility to land within the normal range and, hopefully, be not just liberated from prophylaxis but maybe liberated from the need for factor VIII at all,” Dr. Pipe added. “I think if these AAV platform therapies can’t deliver that on a relatively consistent basis, it’s going to be challenging to get patients to embrace this technology.”

The phase 1/2 trial is sponsored by Bayer in collaboration with Ultragenyx Pharmaceutical Inc. Dr. Pipe disclosed relationships with Bayer and other companies.

jensmith@mdedge.com

SOURCE: Pipe SW et al. EAHAD 2020. Abstract P190.

First-in-human results suggest a gene therapy, BAY 2599023, can increase factor VIII levels in patients with hemophilia A, but it isn’t clear if BAY 2599023 can eliminate the need for prophylaxis.

©designer491/Thinkstock

Of four patients who received BAY 2599023, three achieved clinically meaningful factor VIII levels, and all were able to stop prophylaxis at some point. However, one patient had to resume prophylaxis, and all four have experienced bleeds since receiving BAY 2599023.

This is a dose-escalating trial (NCT03588299), so researchers are still attempting to determine the optimal dose of BAY 2599023. Upcoming results in two patients treated at the highest dose should provide more insight, according to Steven W. Pipe, MD, of the University of Michigan in Ann Arbor.

Dr. Pipe presented results with BAY 2599023 at the annual congress of the European Association for Haemophilia and Allied Disorders.

He noted that between 30% and 70% of hemophilia patients may have preexisting neutralizing antibodies to specific adeno-associated virus (AAV) serotypes. Developing gene therapies with varying serotypes could reduce this problem and increase eligibility for gene therapy. Bayer had this in mind when developing BAY 2599023.

BAY 2599023 is a non-replicating AAV vector, based on the AAV serotype hu37, which contains a single-stranded DNA genome encoding a B-domain deleted factor VIII, under the control of a liver-specific promotor/enhancer combination optimized for transgenic expression, Dr. Pipe explained.

He presented results with BAY 2599023 in four patients with severe hemophilia A. At baseline, patients were receiving prophylaxis and did not have factor VIII inhibitors or detectable immunity to the AAVhu37 capsid.
 

First cohort

Two patients received BAY 2599023 at a dose of 0.5 × 10¹³ GC/kg. One patient achieved a factor VIII level above 5% at this dose and was able to stop prophylaxis temporarily. The patient experienced two bleeds on study and had to resume prophylaxis because of a target joint.

“He came into the study with a particularly challenging target joint in his ankle, and he had known from experience on prophylaxis that, if his factor level got too low, he would have breakthrough bleeds,” Dr. Pipe explained. “So we agreed that if he didn’t achieve a sustained level above 5%, he would go back on prophylaxis. He was able to stay off prophylaxis for 6 weeks, but we had to put him back on because of breakthrough bleeding.”

Dr. Pipe and colleagues have been following this patient for about a year, and the patient still has factor VIII levels of about 2% to 3% after a washout of prophylaxis.

The other patient who received a dose of 0.5 × 10¹³ GC/kg came off prophylaxis early on and has sustained factor VIII levels of 20%. This patient had four bleeds early in the trial but has since done very well, Dr. Pipe said. The patient had 99 bleeds in the year prior to receiving BAY 2599023.
 

Second cohort

Two subsequent patients received BAY 2599023 at a dose of 1 × 10¹³ GC/kg. Both patients have stopped prophylaxis.

One patient achieved factor VIII levels in the 5%-10% range and stopped prophylaxis at day 49. The patient has received on-demand treatment for four bleeds. The other patient achieved “robust” factor VIII expression levels “well above 20%,” according to Dr. Pipe. This patient stopped prophylaxis at day 10 and experienced bleeds early on but has remained bleed-free and treatment-free for 7 months.

Dr. Pipe noted that this patient experienced a spike in transaminases “very early on” after receiving BAY 2599023.

“So he was put on prednisone, but his liver enzymes almost immediately corrected to within the normal range,” Dr. Pipe said. “He has finished the cascading dose of prednisone, his liver enzymes have remained stable, his factor VIII expression has remained stable, and he continues to do very well.”
 

Next steps

Based on results in the first two cohorts, researchers are proceeding with a higher dose of BAY 2599023.

“The overall goal of this study is to identify the optimal dose that can be taken forward to the planned phase 3 study,” Dr. Pipe said. “What they [Bayer] would like to bring to the community is a product that offers a chance for maximum eligibility based on low screen out because of preexisting immunity and maximize the number of patients who are in the normal range.”

“For patients to embrace gene therapy, it really has to get them at least the possibility to land within the normal range and, hopefully, be not just liberated from prophylaxis but maybe liberated from the need for factor VIII at all,” Dr. Pipe added. “I think if these AAV platform therapies can’t deliver that on a relatively consistent basis, it’s going to be challenging to get patients to embrace this technology.”

The phase 1/2 trial is sponsored by Bayer in collaboration with Ultragenyx Pharmaceutical Inc. Dr. Pipe disclosed relationships with Bayer and other companies.

jensmith@mdedge.com

SOURCE: Pipe SW et al. EAHAD 2020. Abstract P190.