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Lorlatinib: Another first-line option for ALK-positive NSCLC?
Lorlatinib also produced a higher overall and intracranial response rate, prolonging progression to CNS disease.
These findings “support the use of lorlatinib as a highly effective first-line therapy for patients with advanced ALK-positive NSCLC,” said Benjamin Solomon, MBBS, PhD, of the Peter MacCallum Cancer Centre in Melbourne.
“The CROWN study clearly establishes lorlatinib as another option” among other first-line ALK inhibitors, Dr. Solomon said when presenting the findings at the European Society for Medical Oncology Virtual Congress 2020.
“We now have multiple options for first-line treatment of patients with ALK-positive lung cancer,” noted study discussant Christine Lovly, MD, PhD, a medical oncologist and associate professor at Vanderbilt University Medical Center in Nashville, Tenn.
The question now, she said, is how to choose among these options. The drugs have all bested crizotinib in trials but haven’t gone head to head against one another.
Lorlatinib and CROWN
Lorlatinib is currently approved in the United States to treat ALK-positive metastatic NSCLC that has progressed on crizotinib and at least one other ALK inhibitor. Lorlatinib was granted accelerated approval for this indication based on response rate and duration.
The CROWN study was intended to support the conversion to full approval, according to Pfizer, which is developing both lorlatinib and crizotinib. Pfizer also plans to use the results of CROWN to seek a first-line indication for lorlatinib in NSCLC.
CROWN enrolled 296 patients with stage IIIB/IV ALK-positive NSCLC who had received no prior systemic treatment. Patients with asymptomatic treated or untreated CNS metastases were eligible.
There were 149 patients randomized to lorlatinib at 100 mg daily and 147 randomized to crizotinib at 250 mg twice daily. Five patients in the crizotinib arm were included in the analysis but were not treated, Dr. Solomon said.
The median age was 61 years in the lorlatinib arm and 56 years in the crizotinib arm. Nearly all patients were White (48% in the lorlatinib arm and 49% in the crizotinib arm) or Asian (44% in both arms). A majority of patients were women (56% in the lorlatinib arm and 62% in the crizotinib arm), and more than half said they never smoked (54% in the lorlatinib arm and 64% in the crizotinib arm).
Response and PFS
According to blinded independent central review, the objective response rate was 76% with lorlatinib (113/149) and 58% with crizotinib (85/147). There were four complete responses with lorlatinib and none with crizotinib.
Among patients who had measurable or nonmeasurable brain metastases at baseline, the intracranial ORR was 66% with lorlatinib (25/38) and 20% (8/40) with crizotinib. In patients with only measurable brain metastases at baseline, the intracranial ORR was 82% with lorlatinib (14/17) and 23% with crizotinib (3/13).
The 12-month PFS rate was 78% in the lorlatinib arm and 39% in the crizotinib arm. The median PFS was 9.3 months in the crizotinib arm but was not reached in the lorlatinib arm, which “corresponded to a 72% reduction in the risk of death or progression [hazard ratio, 0.21; P < .001],” Dr. Solomon said.
“[T]he PFS for alectinib in the first line is approximately 3 years,” Dr. Lovly noted. “We anxiously await additional data for lorlatinib to see how long the PFS will be.”
The median time to intracranial progression was 16.6 months in the crizotinib arm but was not reached in the lorlatinib arm (HR, 0.07; P < .001).
“These data indicate the ability of lorlatinib not only to delay the progression of existing brain metastases, but also to prevent the development of new brain metastases,” Dr. Solomon said.
Dr. Lovly noted that the efficacy of lorlatinib in the brain is “quite compelling,” but other ALK inhibitors have demonstrated similar results.
As for overall survival, the data are still immature. The median overall survival was not reached with lorlatinib or crizotinib (HR, 0.72).
Toxicity
Dr. Solomon noted that lorlatinib “does have a different toxicity profile, compared to other ALK inhibitors.” Specifically, lorlatinib is associated with hypercholesterolemia and hypertriglyceridemia, which have not been seen with other ALK inhibitors.
Lorlatinib is also associated with neurocognitive problems, including inattention, memory impairment, and mild confusion. Mood effects include emotional lability – “someone watching a movie might burst into tears when they wouldn’t have otherwise,” Dr. Solomon said – as well as anxiety and depression.
“So it’s important to tell not just the patient but their family about these things so that they identify when [the events] happen,” Dr. Solomon said. “That’s key because [the events are] completely reversible when you stop the drug. With dose interruption, those effects will resolve.”
Other adverse events that were more common with lorlatinib (a 10% or greater difference in frequency from crizotinib) included edema, weight gain, and peripheral neuropathy. Diarrhea, nausea, fatigue, vision disorders, constipation, and increased liver enzymes were more common with crizotinib. Grade 3-4 adverse events led to discontinuation in fewer than 10% of patients in each arm.
The study was funded by Pfizer, and the investigators included employees. Dr. Solomon is an adviser for Pfizer and other companies, and Dr. Lovly’s industry ties included being both an advisor and speaker for Pfizer.
SOURCE: Solomon B et al. ESMO 2020, Abstract LBA2.
Lorlatinib also produced a higher overall and intracranial response rate, prolonging progression to CNS disease.
These findings “support the use of lorlatinib as a highly effective first-line therapy for patients with advanced ALK-positive NSCLC,” said Benjamin Solomon, MBBS, PhD, of the Peter MacCallum Cancer Centre in Melbourne.
“The CROWN study clearly establishes lorlatinib as another option” among other first-line ALK inhibitors, Dr. Solomon said when presenting the findings at the European Society for Medical Oncology Virtual Congress 2020.
“We now have multiple options for first-line treatment of patients with ALK-positive lung cancer,” noted study discussant Christine Lovly, MD, PhD, a medical oncologist and associate professor at Vanderbilt University Medical Center in Nashville, Tenn.
The question now, she said, is how to choose among these options. The drugs have all bested crizotinib in trials but haven’t gone head to head against one another.
Lorlatinib and CROWN
Lorlatinib is currently approved in the United States to treat ALK-positive metastatic NSCLC that has progressed on crizotinib and at least one other ALK inhibitor. Lorlatinib was granted accelerated approval for this indication based on response rate and duration.
The CROWN study was intended to support the conversion to full approval, according to Pfizer, which is developing both lorlatinib and crizotinib. Pfizer also plans to use the results of CROWN to seek a first-line indication for lorlatinib in NSCLC.
CROWN enrolled 296 patients with stage IIIB/IV ALK-positive NSCLC who had received no prior systemic treatment. Patients with asymptomatic treated or untreated CNS metastases were eligible.
There were 149 patients randomized to lorlatinib at 100 mg daily and 147 randomized to crizotinib at 250 mg twice daily. Five patients in the crizotinib arm were included in the analysis but were not treated, Dr. Solomon said.
The median age was 61 years in the lorlatinib arm and 56 years in the crizotinib arm. Nearly all patients were White (48% in the lorlatinib arm and 49% in the crizotinib arm) or Asian (44% in both arms). A majority of patients were women (56% in the lorlatinib arm and 62% in the crizotinib arm), and more than half said they never smoked (54% in the lorlatinib arm and 64% in the crizotinib arm).
Response and PFS
According to blinded independent central review, the objective response rate was 76% with lorlatinib (113/149) and 58% with crizotinib (85/147). There were four complete responses with lorlatinib and none with crizotinib.
Among patients who had measurable or nonmeasurable brain metastases at baseline, the intracranial ORR was 66% with lorlatinib (25/38) and 20% (8/40) with crizotinib. In patients with only measurable brain metastases at baseline, the intracranial ORR was 82% with lorlatinib (14/17) and 23% with crizotinib (3/13).
The 12-month PFS rate was 78% in the lorlatinib arm and 39% in the crizotinib arm. The median PFS was 9.3 months in the crizotinib arm but was not reached in the lorlatinib arm, which “corresponded to a 72% reduction in the risk of death or progression [hazard ratio, 0.21; P < .001],” Dr. Solomon said.
“[T]he PFS for alectinib in the first line is approximately 3 years,” Dr. Lovly noted. “We anxiously await additional data for lorlatinib to see how long the PFS will be.”
The median time to intracranial progression was 16.6 months in the crizotinib arm but was not reached in the lorlatinib arm (HR, 0.07; P < .001).
“These data indicate the ability of lorlatinib not only to delay the progression of existing brain metastases, but also to prevent the development of new brain metastases,” Dr. Solomon said.
Dr. Lovly noted that the efficacy of lorlatinib in the brain is “quite compelling,” but other ALK inhibitors have demonstrated similar results.
As for overall survival, the data are still immature. The median overall survival was not reached with lorlatinib or crizotinib (HR, 0.72).
Toxicity
Dr. Solomon noted that lorlatinib “does have a different toxicity profile, compared to other ALK inhibitors.” Specifically, lorlatinib is associated with hypercholesterolemia and hypertriglyceridemia, which have not been seen with other ALK inhibitors.
Lorlatinib is also associated with neurocognitive problems, including inattention, memory impairment, and mild confusion. Mood effects include emotional lability – “someone watching a movie might burst into tears when they wouldn’t have otherwise,” Dr. Solomon said – as well as anxiety and depression.
“So it’s important to tell not just the patient but their family about these things so that they identify when [the events] happen,” Dr. Solomon said. “That’s key because [the events are] completely reversible when you stop the drug. With dose interruption, those effects will resolve.”
Other adverse events that were more common with lorlatinib (a 10% or greater difference in frequency from crizotinib) included edema, weight gain, and peripheral neuropathy. Diarrhea, nausea, fatigue, vision disorders, constipation, and increased liver enzymes were more common with crizotinib. Grade 3-4 adverse events led to discontinuation in fewer than 10% of patients in each arm.
The study was funded by Pfizer, and the investigators included employees. Dr. Solomon is an adviser for Pfizer and other companies, and Dr. Lovly’s industry ties included being both an advisor and speaker for Pfizer.
SOURCE: Solomon B et al. ESMO 2020, Abstract LBA2.
Lorlatinib also produced a higher overall and intracranial response rate, prolonging progression to CNS disease.
These findings “support the use of lorlatinib as a highly effective first-line therapy for patients with advanced ALK-positive NSCLC,” said Benjamin Solomon, MBBS, PhD, of the Peter MacCallum Cancer Centre in Melbourne.
“The CROWN study clearly establishes lorlatinib as another option” among other first-line ALK inhibitors, Dr. Solomon said when presenting the findings at the European Society for Medical Oncology Virtual Congress 2020.
“We now have multiple options for first-line treatment of patients with ALK-positive lung cancer,” noted study discussant Christine Lovly, MD, PhD, a medical oncologist and associate professor at Vanderbilt University Medical Center in Nashville, Tenn.
The question now, she said, is how to choose among these options. The drugs have all bested crizotinib in trials but haven’t gone head to head against one another.
Lorlatinib and CROWN
Lorlatinib is currently approved in the United States to treat ALK-positive metastatic NSCLC that has progressed on crizotinib and at least one other ALK inhibitor. Lorlatinib was granted accelerated approval for this indication based on response rate and duration.
The CROWN study was intended to support the conversion to full approval, according to Pfizer, which is developing both lorlatinib and crizotinib. Pfizer also plans to use the results of CROWN to seek a first-line indication for lorlatinib in NSCLC.
CROWN enrolled 296 patients with stage IIIB/IV ALK-positive NSCLC who had received no prior systemic treatment. Patients with asymptomatic treated or untreated CNS metastases were eligible.
There were 149 patients randomized to lorlatinib at 100 mg daily and 147 randomized to crizotinib at 250 mg twice daily. Five patients in the crizotinib arm were included in the analysis but were not treated, Dr. Solomon said.
The median age was 61 years in the lorlatinib arm and 56 years in the crizotinib arm. Nearly all patients were White (48% in the lorlatinib arm and 49% in the crizotinib arm) or Asian (44% in both arms). A majority of patients were women (56% in the lorlatinib arm and 62% in the crizotinib arm), and more than half said they never smoked (54% in the lorlatinib arm and 64% in the crizotinib arm).
Response and PFS
According to blinded independent central review, the objective response rate was 76% with lorlatinib (113/149) and 58% with crizotinib (85/147). There were four complete responses with lorlatinib and none with crizotinib.
Among patients who had measurable or nonmeasurable brain metastases at baseline, the intracranial ORR was 66% with lorlatinib (25/38) and 20% (8/40) with crizotinib. In patients with only measurable brain metastases at baseline, the intracranial ORR was 82% with lorlatinib (14/17) and 23% with crizotinib (3/13).
The 12-month PFS rate was 78% in the lorlatinib arm and 39% in the crizotinib arm. The median PFS was 9.3 months in the crizotinib arm but was not reached in the lorlatinib arm, which “corresponded to a 72% reduction in the risk of death or progression [hazard ratio, 0.21; P < .001],” Dr. Solomon said.
“[T]he PFS for alectinib in the first line is approximately 3 years,” Dr. Lovly noted. “We anxiously await additional data for lorlatinib to see how long the PFS will be.”
The median time to intracranial progression was 16.6 months in the crizotinib arm but was not reached in the lorlatinib arm (HR, 0.07; P < .001).
“These data indicate the ability of lorlatinib not only to delay the progression of existing brain metastases, but also to prevent the development of new brain metastases,” Dr. Solomon said.
Dr. Lovly noted that the efficacy of lorlatinib in the brain is “quite compelling,” but other ALK inhibitors have demonstrated similar results.
As for overall survival, the data are still immature. The median overall survival was not reached with lorlatinib or crizotinib (HR, 0.72).
Toxicity
Dr. Solomon noted that lorlatinib “does have a different toxicity profile, compared to other ALK inhibitors.” Specifically, lorlatinib is associated with hypercholesterolemia and hypertriglyceridemia, which have not been seen with other ALK inhibitors.
Lorlatinib is also associated with neurocognitive problems, including inattention, memory impairment, and mild confusion. Mood effects include emotional lability – “someone watching a movie might burst into tears when they wouldn’t have otherwise,” Dr. Solomon said – as well as anxiety and depression.
“So it’s important to tell not just the patient but their family about these things so that they identify when [the events] happen,” Dr. Solomon said. “That’s key because [the events are] completely reversible when you stop the drug. With dose interruption, those effects will resolve.”
Other adverse events that were more common with lorlatinib (a 10% or greater difference in frequency from crizotinib) included edema, weight gain, and peripheral neuropathy. Diarrhea, nausea, fatigue, vision disorders, constipation, and increased liver enzymes were more common with crizotinib. Grade 3-4 adverse events led to discontinuation in fewer than 10% of patients in each arm.
The study was funded by Pfizer, and the investigators included employees. Dr. Solomon is an adviser for Pfizer and other companies, and Dr. Lovly’s industry ties included being both an advisor and speaker for Pfizer.
SOURCE: Solomon B et al. ESMO 2020, Abstract LBA2.
FROM ESMO 2020
No benefit with postoperative radiotherapy in stage IIIAN2 NSCLC
In patients with completely resected non–small cell lung cancer and proven N2 disease, postoperative radiotherapy (PORT) provided no significant improvement in disease-free survival (DFS) at 3 years, according to a phase 3 trial.
Investigator Cécile Le Péchoux, MD, a radiation oncologist from Institut Gustave Roussy in Paris, presented the results of the Lung ART trial at the European Society for Medical Oncology Virtual Congress 2020.
The results resolve what ESMO commentator Rafal Dziadziuszko, MD, PhD, of Medical University of Gdansk (Poland), called “perhaps the longest ongoing debate in thoracic oncology,” on whether or not to irradiate patients with mediastinal lymph node involvement after surgery.
Dr. Dziadziuszko noted that some past studies have suggested PORT may provide improved local control and a survival benefit, but other studies have shown no survival benefit and evidence of harm with PORT.
“So here is an academic study with the answer,” Dr. Dziadziuszko said.
Study details
The intention-to-treat population of Lung ART included 252 patients randomized to receive 5.5 weeks of PORT (54 Gy) and 249 patients randomized to the control arm without PORT.
The patients’ median age was 61 years, 66% were men, and adenocarcinoma was the predominant histology (76% of patients in the control arm and 70% in the PORT arm). All patients had received adjuvant or neoadjuvant chemotherapy.
The median follow-up was 4.8 years. The 3-year DFS rate was 47.1% in the PORT arm and 43.8% in the control arm (hazard ratio, 0.85; 95% confidence interval, 0.67-1.07, P = .16). The median DFS was 30.5 months with PORT and 22.8 months in the control group. As for DFS components, the rate for death as a first event was 14.6% in the PORT arm and 5.3% among controls.
The mediastinal relapse rate was higher among controls, at 46.1% versus 25.0% with PORT.
The 3-year overall survival rate was 66.5% among patients in the PORT arm and 68.5% in the control arm.
At least one grade 3-4 toxicity was reported in 23.7% of the PORT group and in 15.0% of controls. The grade 3-4 cardiopulmonary toxicity rate of 10.8% in the PORT arm and 4.9% in the control arm needs to be further explored, Dr. Le Péchoux said.
Applying the results to practice
In response to a question as to which patients might benefit from PORT, Dr. Le Péchoux pointed out that, among patients who have nodes in the inferior part of the mediastinum closer to the heart, PORT might be more toxic.
“For the moment, we did not see anything that would give us a clue,” Dr. Le Péchoux said. “We have a lot to investigate.”
Further analyses looking at patterns of failure, predictive factors of efficacy and toxicity, quality of radiotherapy, and quality of surgery are planned, she added.
Dr. Le Péchoux concluded: “Conformal PORT cannot be recommended as standard of care in all completely resected stage IIIAN2 [non–small cell lung cancer] patients.”
Dr. Dziadziuszko commented further: “For my practice, this is a clear message that routine PORT should not be used in these patients. We are looking for more effective systemic therapies.”
He added that “over 50% 5-year survival in these patients is a great result, and is made possible by modern staging and modern surgery.”
The Lung ART study was sponsored by Gustave Roussy and supported by the French National Cancer Institute, French Health Ministry, and a Cancer Research UK grant. Dr. Le Péchoux and Dr. Dziadziuszko reported no conflicts of interest related to the presentation.
SOURCE: Le Péchoux C et al. ESMO 2020, Abstract LBA3_PR.
In patients with completely resected non–small cell lung cancer and proven N2 disease, postoperative radiotherapy (PORT) provided no significant improvement in disease-free survival (DFS) at 3 years, according to a phase 3 trial.
Investigator Cécile Le Péchoux, MD, a radiation oncologist from Institut Gustave Roussy in Paris, presented the results of the Lung ART trial at the European Society for Medical Oncology Virtual Congress 2020.
The results resolve what ESMO commentator Rafal Dziadziuszko, MD, PhD, of Medical University of Gdansk (Poland), called “perhaps the longest ongoing debate in thoracic oncology,” on whether or not to irradiate patients with mediastinal lymph node involvement after surgery.
Dr. Dziadziuszko noted that some past studies have suggested PORT may provide improved local control and a survival benefit, but other studies have shown no survival benefit and evidence of harm with PORT.
“So here is an academic study with the answer,” Dr. Dziadziuszko said.
Study details
The intention-to-treat population of Lung ART included 252 patients randomized to receive 5.5 weeks of PORT (54 Gy) and 249 patients randomized to the control arm without PORT.
The patients’ median age was 61 years, 66% were men, and adenocarcinoma was the predominant histology (76% of patients in the control arm and 70% in the PORT arm). All patients had received adjuvant or neoadjuvant chemotherapy.
The median follow-up was 4.8 years. The 3-year DFS rate was 47.1% in the PORT arm and 43.8% in the control arm (hazard ratio, 0.85; 95% confidence interval, 0.67-1.07, P = .16). The median DFS was 30.5 months with PORT and 22.8 months in the control group. As for DFS components, the rate for death as a first event was 14.6% in the PORT arm and 5.3% among controls.
The mediastinal relapse rate was higher among controls, at 46.1% versus 25.0% with PORT.
The 3-year overall survival rate was 66.5% among patients in the PORT arm and 68.5% in the control arm.
At least one grade 3-4 toxicity was reported in 23.7% of the PORT group and in 15.0% of controls. The grade 3-4 cardiopulmonary toxicity rate of 10.8% in the PORT arm and 4.9% in the control arm needs to be further explored, Dr. Le Péchoux said.
Applying the results to practice
In response to a question as to which patients might benefit from PORT, Dr. Le Péchoux pointed out that, among patients who have nodes in the inferior part of the mediastinum closer to the heart, PORT might be more toxic.
“For the moment, we did not see anything that would give us a clue,” Dr. Le Péchoux said. “We have a lot to investigate.”
Further analyses looking at patterns of failure, predictive factors of efficacy and toxicity, quality of radiotherapy, and quality of surgery are planned, she added.
Dr. Le Péchoux concluded: “Conformal PORT cannot be recommended as standard of care in all completely resected stage IIIAN2 [non–small cell lung cancer] patients.”
Dr. Dziadziuszko commented further: “For my practice, this is a clear message that routine PORT should not be used in these patients. We are looking for more effective systemic therapies.”
He added that “over 50% 5-year survival in these patients is a great result, and is made possible by modern staging and modern surgery.”
The Lung ART study was sponsored by Gustave Roussy and supported by the French National Cancer Institute, French Health Ministry, and a Cancer Research UK grant. Dr. Le Péchoux and Dr. Dziadziuszko reported no conflicts of interest related to the presentation.
SOURCE: Le Péchoux C et al. ESMO 2020, Abstract LBA3_PR.
In patients with completely resected non–small cell lung cancer and proven N2 disease, postoperative radiotherapy (PORT) provided no significant improvement in disease-free survival (DFS) at 3 years, according to a phase 3 trial.
Investigator Cécile Le Péchoux, MD, a radiation oncologist from Institut Gustave Roussy in Paris, presented the results of the Lung ART trial at the European Society for Medical Oncology Virtual Congress 2020.
The results resolve what ESMO commentator Rafal Dziadziuszko, MD, PhD, of Medical University of Gdansk (Poland), called “perhaps the longest ongoing debate in thoracic oncology,” on whether or not to irradiate patients with mediastinal lymph node involvement after surgery.
Dr. Dziadziuszko noted that some past studies have suggested PORT may provide improved local control and a survival benefit, but other studies have shown no survival benefit and evidence of harm with PORT.
“So here is an academic study with the answer,” Dr. Dziadziuszko said.
Study details
The intention-to-treat population of Lung ART included 252 patients randomized to receive 5.5 weeks of PORT (54 Gy) and 249 patients randomized to the control arm without PORT.
The patients’ median age was 61 years, 66% were men, and adenocarcinoma was the predominant histology (76% of patients in the control arm and 70% in the PORT arm). All patients had received adjuvant or neoadjuvant chemotherapy.
The median follow-up was 4.8 years. The 3-year DFS rate was 47.1% in the PORT arm and 43.8% in the control arm (hazard ratio, 0.85; 95% confidence interval, 0.67-1.07, P = .16). The median DFS was 30.5 months with PORT and 22.8 months in the control group. As for DFS components, the rate for death as a first event was 14.6% in the PORT arm and 5.3% among controls.
The mediastinal relapse rate was higher among controls, at 46.1% versus 25.0% with PORT.
The 3-year overall survival rate was 66.5% among patients in the PORT arm and 68.5% in the control arm.
At least one grade 3-4 toxicity was reported in 23.7% of the PORT group and in 15.0% of controls. The grade 3-4 cardiopulmonary toxicity rate of 10.8% in the PORT arm and 4.9% in the control arm needs to be further explored, Dr. Le Péchoux said.
Applying the results to practice
In response to a question as to which patients might benefit from PORT, Dr. Le Péchoux pointed out that, among patients who have nodes in the inferior part of the mediastinum closer to the heart, PORT might be more toxic.
“For the moment, we did not see anything that would give us a clue,” Dr. Le Péchoux said. “We have a lot to investigate.”
Further analyses looking at patterns of failure, predictive factors of efficacy and toxicity, quality of radiotherapy, and quality of surgery are planned, she added.
Dr. Le Péchoux concluded: “Conformal PORT cannot be recommended as standard of care in all completely resected stage IIIAN2 [non–small cell lung cancer] patients.”
Dr. Dziadziuszko commented further: “For my practice, this is a clear message that routine PORT should not be used in these patients. We are looking for more effective systemic therapies.”
He added that “over 50% 5-year survival in these patients is a great result, and is made possible by modern staging and modern surgery.”
The Lung ART study was sponsored by Gustave Roussy and supported by the French National Cancer Institute, French Health Ministry, and a Cancer Research UK grant. Dr. Le Péchoux and Dr. Dziadziuszko reported no conflicts of interest related to the presentation.
SOURCE: Le Péchoux C et al. ESMO 2020, Abstract LBA3_PR.
FROM ESMO 2020
Survey quantifies COVID-19’s impact on oncology
An international survey provides new insights into how COVID-19 has affected, and may continue to affect, the field of oncology.
The survey showed that “COVID-19 has had a major impact on the organization of patient care, on the well-being of caregivers, on continued medical education, and on clinical trial activities in oncology,” stated Guy Jerusalem, MD, PhD, of Centre Hospitalier Universitaire de Liège (Belgium).
Dr. Jerusalem presented these findings at the European Society for Medical Oncology Virtual Congress 2020.
The survey was distributed by 20 oncologists from 10 of the countries most affected by COVID-19. Responses were obtained from 109 oncologists representing centers in 18 countries. The responses were recorded between June 17 and July 14, 2020.
The survey consisted of 95 items intended to evaluate the impact of COVID-19 on the organization of oncologic care. Questions encompassed the capacity and service offered at each center, the magnitude of COVID-19–based care interruptions and the reasons for them, the ensuing challenges faced, interventions implemented, and the estimated harms to patients during the pandemic.
The 109 oncologists surveyed had a median of 20 years of oncology experience. A majority of respondents were men (61.5%), and the median age was 48.5 years.
The respondents had worked predominantly (62.4%) at academic hospitals, with 29.6% at community hospitals. Most respondents worked at general hospitals with an oncology unit (66.1%) rather than a specialized separate cancer center (32.1%).
The most common specialty was breast cancer (60.6%), followed by gastrointestinal cancer (10.1%), urogenital cancer (9.2%), and lung cancer (8.3%).
Impact on treatment
The treatment modalities affected by the pandemic – through cancellations or delays in more than 10% of patients – included surgery (in 34% of centers), chemotherapy (22%), radiotherapy (13.7%), checkpoint inhibitor therapy (9.1%), monoclonal antibodies (9%), and oral targeted therapy (3.7%).
Among oncologists treating breast cancer, cancellations/delays in more than 10% of patients were reported for everolimus (18%), CDK4/6 inhibitors (8.9%), and endocrine therapy (2.2%).
Overall, 34.8% of respondents reported increased use of granulocyte colony–stimulating factor, and 6.4% reported increased use of erythropoietin.
On the other hand, 11.1% of respondents reported a decrease in the use of double immunotherapy, and 21.9% reported decreased use of corticosteroids.
Not only can the immunosuppressive effects of steroid use increase infection risks, Dr. Jerusalem noted, fever suppression can lead to a delayed diagnosis of COVID-19.
“To circumvent potential higher infection risks or greater disease severity, we use lower doses of steroids, but this is not based on studies,” he said.
“Previous exposure to steroids or being on steroids at the time of COVID-19 infection is a detrimental factor for complications and mortality,” commented ESMO President Solange Peters, MD, PhD, of Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland.
Dr. Peters noted that the observation was based on lung cancer registry findings. Furthermore, because data from smaller outbreaks of other coronavirus infections suggested worse prognosis and increased mortality, steroid use was already feared in the very early days of the COVID-19 pandemic.
Lastly, earlier cessation of palliative treatment was observed in 32.1% of centers, and 64.2% of respondents agreed that undertreatment because of COVID-19 is a major concern.
Dr. Jerusalem noted that the survey data do not explain the early cessation of palliative treatment. “I suspect that many patients died at home rather than alone in institutions because it was the only way they could die with their families around them.”
Telehealth, meetings, and trials
The survey also revealed rationales for the use of teleconsultation, including follow-up (94.5%), oral therapy (92.7%), immunotherapy (57.8%), and chemotherapy (55%).
Most respondents reported more frequent use of virtual meetings for continuing medical education (94%), oncologic team meetings (92%), and tumor boards (82%).
While about 82% of respondents said they were likely to continue the use of telemedicine, 45% said virtual conferences are not an acceptable alternative to live international conferences such as ESMO, Dr. Jerusalem said.
Finally, nearly three-quarters of respondents (72.5%) said all clinical trial activities are or will soon be activated, or never stopped, at their centers. On the other hand, 27.5% of respondents reported that their centers had major protocol violations or deviations, and 37% of respondents said they expect significant reductions in clinical trial activities this year.
Dr. Jerusalem concluded that COVID-19 is having a major, long-term impact on the organization of patient care, caregivers, continued medical education, and clinical trial activities in oncology.
He cautioned that “the risk of a delayed diagnosis of new cancers and economic consequences of COVID-19 on access to health care and cancer treatments have to be carefully evaluated.”
This research was funded by Fondation Léon Fredericq. Dr. Jerusalem disclosed relationships with Novartis, Roche, Lilly, Pfizer, Amgen, Bristol-Myers Squibb, AstraZeneca, Daiichi Sankyo, AbbVie, MedImmune, and Merck. Dr. Peters disclosed relationships with AbbVie, Amgen, AstraZeneca, and many other companies.
SOURCE: Jerusalem G et al. ESMO 2020, Abstract LBA76.
An international survey provides new insights into how COVID-19 has affected, and may continue to affect, the field of oncology.
The survey showed that “COVID-19 has had a major impact on the organization of patient care, on the well-being of caregivers, on continued medical education, and on clinical trial activities in oncology,” stated Guy Jerusalem, MD, PhD, of Centre Hospitalier Universitaire de Liège (Belgium).
Dr. Jerusalem presented these findings at the European Society for Medical Oncology Virtual Congress 2020.
The survey was distributed by 20 oncologists from 10 of the countries most affected by COVID-19. Responses were obtained from 109 oncologists representing centers in 18 countries. The responses were recorded between June 17 and July 14, 2020.
The survey consisted of 95 items intended to evaluate the impact of COVID-19 on the organization of oncologic care. Questions encompassed the capacity and service offered at each center, the magnitude of COVID-19–based care interruptions and the reasons for them, the ensuing challenges faced, interventions implemented, and the estimated harms to patients during the pandemic.
The 109 oncologists surveyed had a median of 20 years of oncology experience. A majority of respondents were men (61.5%), and the median age was 48.5 years.
The respondents had worked predominantly (62.4%) at academic hospitals, with 29.6% at community hospitals. Most respondents worked at general hospitals with an oncology unit (66.1%) rather than a specialized separate cancer center (32.1%).
The most common specialty was breast cancer (60.6%), followed by gastrointestinal cancer (10.1%), urogenital cancer (9.2%), and lung cancer (8.3%).
Impact on treatment
The treatment modalities affected by the pandemic – through cancellations or delays in more than 10% of patients – included surgery (in 34% of centers), chemotherapy (22%), radiotherapy (13.7%), checkpoint inhibitor therapy (9.1%), monoclonal antibodies (9%), and oral targeted therapy (3.7%).
Among oncologists treating breast cancer, cancellations/delays in more than 10% of patients were reported for everolimus (18%), CDK4/6 inhibitors (8.9%), and endocrine therapy (2.2%).
Overall, 34.8% of respondents reported increased use of granulocyte colony–stimulating factor, and 6.4% reported increased use of erythropoietin.
On the other hand, 11.1% of respondents reported a decrease in the use of double immunotherapy, and 21.9% reported decreased use of corticosteroids.
Not only can the immunosuppressive effects of steroid use increase infection risks, Dr. Jerusalem noted, fever suppression can lead to a delayed diagnosis of COVID-19.
“To circumvent potential higher infection risks or greater disease severity, we use lower doses of steroids, but this is not based on studies,” he said.
“Previous exposure to steroids or being on steroids at the time of COVID-19 infection is a detrimental factor for complications and mortality,” commented ESMO President Solange Peters, MD, PhD, of Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland.
Dr. Peters noted that the observation was based on lung cancer registry findings. Furthermore, because data from smaller outbreaks of other coronavirus infections suggested worse prognosis and increased mortality, steroid use was already feared in the very early days of the COVID-19 pandemic.
Lastly, earlier cessation of palliative treatment was observed in 32.1% of centers, and 64.2% of respondents agreed that undertreatment because of COVID-19 is a major concern.
Dr. Jerusalem noted that the survey data do not explain the early cessation of palliative treatment. “I suspect that many patients died at home rather than alone in institutions because it was the only way they could die with their families around them.”
Telehealth, meetings, and trials
The survey also revealed rationales for the use of teleconsultation, including follow-up (94.5%), oral therapy (92.7%), immunotherapy (57.8%), and chemotherapy (55%).
Most respondents reported more frequent use of virtual meetings for continuing medical education (94%), oncologic team meetings (92%), and tumor boards (82%).
While about 82% of respondents said they were likely to continue the use of telemedicine, 45% said virtual conferences are not an acceptable alternative to live international conferences such as ESMO, Dr. Jerusalem said.
Finally, nearly three-quarters of respondents (72.5%) said all clinical trial activities are or will soon be activated, or never stopped, at their centers. On the other hand, 27.5% of respondents reported that their centers had major protocol violations or deviations, and 37% of respondents said they expect significant reductions in clinical trial activities this year.
Dr. Jerusalem concluded that COVID-19 is having a major, long-term impact on the organization of patient care, caregivers, continued medical education, and clinical trial activities in oncology.
He cautioned that “the risk of a delayed diagnosis of new cancers and economic consequences of COVID-19 on access to health care and cancer treatments have to be carefully evaluated.”
This research was funded by Fondation Léon Fredericq. Dr. Jerusalem disclosed relationships with Novartis, Roche, Lilly, Pfizer, Amgen, Bristol-Myers Squibb, AstraZeneca, Daiichi Sankyo, AbbVie, MedImmune, and Merck. Dr. Peters disclosed relationships with AbbVie, Amgen, AstraZeneca, and many other companies.
SOURCE: Jerusalem G et al. ESMO 2020, Abstract LBA76.
An international survey provides new insights into how COVID-19 has affected, and may continue to affect, the field of oncology.
The survey showed that “COVID-19 has had a major impact on the organization of patient care, on the well-being of caregivers, on continued medical education, and on clinical trial activities in oncology,” stated Guy Jerusalem, MD, PhD, of Centre Hospitalier Universitaire de Liège (Belgium).
Dr. Jerusalem presented these findings at the European Society for Medical Oncology Virtual Congress 2020.
The survey was distributed by 20 oncologists from 10 of the countries most affected by COVID-19. Responses were obtained from 109 oncologists representing centers in 18 countries. The responses were recorded between June 17 and July 14, 2020.
The survey consisted of 95 items intended to evaluate the impact of COVID-19 on the organization of oncologic care. Questions encompassed the capacity and service offered at each center, the magnitude of COVID-19–based care interruptions and the reasons for them, the ensuing challenges faced, interventions implemented, and the estimated harms to patients during the pandemic.
The 109 oncologists surveyed had a median of 20 years of oncology experience. A majority of respondents were men (61.5%), and the median age was 48.5 years.
The respondents had worked predominantly (62.4%) at academic hospitals, with 29.6% at community hospitals. Most respondents worked at general hospitals with an oncology unit (66.1%) rather than a specialized separate cancer center (32.1%).
The most common specialty was breast cancer (60.6%), followed by gastrointestinal cancer (10.1%), urogenital cancer (9.2%), and lung cancer (8.3%).
Impact on treatment
The treatment modalities affected by the pandemic – through cancellations or delays in more than 10% of patients – included surgery (in 34% of centers), chemotherapy (22%), radiotherapy (13.7%), checkpoint inhibitor therapy (9.1%), monoclonal antibodies (9%), and oral targeted therapy (3.7%).
Among oncologists treating breast cancer, cancellations/delays in more than 10% of patients were reported for everolimus (18%), CDK4/6 inhibitors (8.9%), and endocrine therapy (2.2%).
Overall, 34.8% of respondents reported increased use of granulocyte colony–stimulating factor, and 6.4% reported increased use of erythropoietin.
On the other hand, 11.1% of respondents reported a decrease in the use of double immunotherapy, and 21.9% reported decreased use of corticosteroids.
Not only can the immunosuppressive effects of steroid use increase infection risks, Dr. Jerusalem noted, fever suppression can lead to a delayed diagnosis of COVID-19.
“To circumvent potential higher infection risks or greater disease severity, we use lower doses of steroids, but this is not based on studies,” he said.
“Previous exposure to steroids or being on steroids at the time of COVID-19 infection is a detrimental factor for complications and mortality,” commented ESMO President Solange Peters, MD, PhD, of Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland.
Dr. Peters noted that the observation was based on lung cancer registry findings. Furthermore, because data from smaller outbreaks of other coronavirus infections suggested worse prognosis and increased mortality, steroid use was already feared in the very early days of the COVID-19 pandemic.
Lastly, earlier cessation of palliative treatment was observed in 32.1% of centers, and 64.2% of respondents agreed that undertreatment because of COVID-19 is a major concern.
Dr. Jerusalem noted that the survey data do not explain the early cessation of palliative treatment. “I suspect that many patients died at home rather than alone in institutions because it was the only way they could die with their families around them.”
Telehealth, meetings, and trials
The survey also revealed rationales for the use of teleconsultation, including follow-up (94.5%), oral therapy (92.7%), immunotherapy (57.8%), and chemotherapy (55%).
Most respondents reported more frequent use of virtual meetings for continuing medical education (94%), oncologic team meetings (92%), and tumor boards (82%).
While about 82% of respondents said they were likely to continue the use of telemedicine, 45% said virtual conferences are not an acceptable alternative to live international conferences such as ESMO, Dr. Jerusalem said.
Finally, nearly three-quarters of respondents (72.5%) said all clinical trial activities are or will soon be activated, or never stopped, at their centers. On the other hand, 27.5% of respondents reported that their centers had major protocol violations or deviations, and 37% of respondents said they expect significant reductions in clinical trial activities this year.
Dr. Jerusalem concluded that COVID-19 is having a major, long-term impact on the organization of patient care, caregivers, continued medical education, and clinical trial activities in oncology.
He cautioned that “the risk of a delayed diagnosis of new cancers and economic consequences of COVID-19 on access to health care and cancer treatments have to be carefully evaluated.”
This research was funded by Fondation Léon Fredericq. Dr. Jerusalem disclosed relationships with Novartis, Roche, Lilly, Pfizer, Amgen, Bristol-Myers Squibb, AstraZeneca, Daiichi Sankyo, AbbVie, MedImmune, and Merck. Dr. Peters disclosed relationships with AbbVie, Amgen, AstraZeneca, and many other companies.
SOURCE: Jerusalem G et al. ESMO 2020, Abstract LBA76.
FROM ESMO 2020
COVID-19 prompts ‘democratization’ of cancer trials
The pandemic has taught researchers how to decentralize trials, which should not only improve patient satisfaction but increase trial accrual by providing access to typically underserved populations, Patricia M. LoRusso, DO, of Yale University, New Haven, Conn., said at the meeting.
Dr. LoRusso was one of six panelists who participated in a forum about changes to cancer trials that were prompted by the pandemic. The forum was moderated by Keith T. Flaherty, MD, of Massachusetts General Hospital in Boston.
Dr. Flaherty asked the panelists to explain adjustments their organizations have made in response to the pandemic, discuss accomplishments, and speculate on future challenges and priorities.
Trial, administrative, and patient-care modifications
COVID-19 put some cancer trials on hold. For others, the pandemic forced sponsors and study chairs to reduce trial complexity and identify nonessential aspects of the studies, according to panelist José Baselga, MD, PhD, of AstraZeneca.
Specifically, exploratory objectives were subjugated to patient safety and a focus on the primary endpoints of each trial.
Once the critical data were identified, study chairs were asked to determine whether data could be obtained through technologies that could substitute for face-to-face contact between patients and staff – for example, patient-reported outcome tools and at-home digital monitoring.
Modifications prompted by the pandemic include the following:
- On-site auditing was suspended.
- Oral investigational agents were shipped directly to patients.
- “Remote” informed consent (telephone or video consenting) was permitted.
- Local providers could perform study-related services, with oversight by the research site.
- Minor deviations from the written protocols were allowed, provided the deviations did not affect patient care or data integrity.
“Obviously, the pandemic has been horrible, but what it has allowed us to do, as investigators in the clinical research landscape, … is to change our focus somewhat and realize, first and foremost, the patient is at the center of this,” Dr. LoRusso said.
Operational accomplishments and benefits
The pandemic caused a 40% decline in accrual to studies supported by the National Cancer Institute’s (NCI) Clinical Trials Network (NCTN) from mid-March to early April, according to James H. Doroshow, MD, of NCI.
However, after modifications to administrative and regulatory procedures, accrual to NCTN trials recovered to approximately 80% of prepandemic levels, Dr. Doroshow said.
The pandemic prompted investigators to leverage tools and technology they had not previously used frequently or at all, the panelists pointed out.
Investigators discovered perforce that telehealth could be used for almost all trial-related assessments. In lieu of physical examination, patients could send pictures of rashes and use electronic devices to monitor blood sugar values and vital signs.
Digital radiographic studies were performed at sites that were most convenient for patients, downloaded, and reinterpreted at the study institution. Visiting nurses and neighborhood laboratories enabled less-frequent in-person visits for assessments.
These adjustments have been particularly important for geographically and/or socioeconomically disadvantaged patients, the panelists said.
Overall, there was agreement among the panelists that shared values and trust among regulatory authorities, sponsors, investigators, and clinicians were impressive in their urgency, sincerity, and patient centricity.
“This pandemic … has forced us to think differently and be nimble and creative to our approach to maintaining our overriding goals while at the same time bringing these innovative therapies forward for patients with cancer and other serious and life-threatening diseases as quickly as possible,” said panelist Kristen M. Hege, MD, of Bristol-Myers Squibb.
In fact, Dr. Hege noted, some cancer-related therapies (e.g., BTK inhibitors, JAK inhibitors, and immunomodulatory agents) were “repurposed” rapidly and tested against COVID-related complications.
Streamlining trial regulatory processes
In addition to changing ongoing trials, the pandemic has affected how new research projects are launched.
One new study that came together quickly in response to the pandemic is the NCI COVID-19 in Cancer Patients Study (NCCAPS). NCCAPS is a natural history study with biospecimens and an imaging library. It was approved in just 5 weeks and is active in 650 sites, with “gangbusters” accrual, Dr. Doroshow said.
The rapidness of NCCAPS’ design and implementation should prompt the revision of previously accepted timelines for trial activation and lead to streamlined future processes.
Another project that was launched quickly in response to the pandemic is the COVID-19 evidence accelerator, according to Paul G. Kluetz, MD, of the Food and Drug Administration.
The COVID-19 evidence accelerator integrates real-world evidence into a database to provide investigators and health systems with the ability to gather information, design rapid turnaround queries, and share results. The evidence accelerator can provide study chairs with information that may have relevance to the safety of participants in clinical trials.
Future directions and challenges
The panelists agreed that pandemic-related modifications in processes will not only accelerate trial approval and activation but should facilitate higher study accrual, increase the diversity of protocol participants, and decrease the costs associated with clinical trial conduct.
With that in mind, the NCI is planning randomized clinical trials in which “process A” is compared with “process B,” Dr. Doroshow said. The goal is to determine which modifications are most likely to make trials available to patients without compromising data integrity or patient safety.
“How much less data do you need to have an outcome that will be similar?” Dr. Doroshow asked. “How many fewer visits, how many fewer tests, how much can you save? Physicians, clinical trialists, all of us respond to data, and if you get the same outcome at a third of the cost, then everybody benefits.”
Nonetheless, we will need to be vigilant for unintended vulnerabilities from well-intended efforts, according to Dr. Kluetz. Study chairs, sponsors, and regulatory agencies will need to be attentive to whether there are important differences in scan quality or interpretation, missing data that influence trial outcomes, and so on.
Dr. Hege pointed out that differences among data sources may be less important when treatments generate large effects but may be vitally important when the relative differences among treatments are small.
On a practical level, decentralizing clinical research may negatively impact the finances of tertiary care centers, which could threaten the required infrastructure for clinical trials, a few panelists noted.
The relative balance of NCI-, industry-, and investigator-initiated trials may require adjustment so that research income is adequate to maintain the costs associated with cancer clinical trials.
Shared goals and democratization
The pandemic has required all stakeholders in clinical research to rely on relationships of trust and shared goals, said Caroline Robert, MD, PhD, of Institut Gustave Roussy in Villejuif, France.
Dr. Kluetz summarized those goals as improving trial efficiencies, decreasing patient burden, decentralizing trials, and maintaining trial integrity.
A decentralized clinical trials operational model could lead to better generalizability of study outcomes, normalization of life for patients on studies, and lower costs of trial conduct. As such, decentralization would promote democratization.
Coupled with ongoing efforts to reduce eligibility criteria in cancer trials, the pandemic has brought operational solutions that should be perpetuated and has reminded us of the interlocking and mutually supportive relationships on which clinical research success depends.
Dr. Doroshow and Dr. Kluetz disclosed no conflicts of interest. All other panelists disclosed financial relationships, including employment, with a range of companies.
Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.
SOURCE: Flaherty KT et al. AACR: COVID-19 and Cancer, Regulatory and Operational Implications of Cancer Clinical Trial Changes During COVID-19.
The pandemic has taught researchers how to decentralize trials, which should not only improve patient satisfaction but increase trial accrual by providing access to typically underserved populations, Patricia M. LoRusso, DO, of Yale University, New Haven, Conn., said at the meeting.
Dr. LoRusso was one of six panelists who participated in a forum about changes to cancer trials that were prompted by the pandemic. The forum was moderated by Keith T. Flaherty, MD, of Massachusetts General Hospital in Boston.
Dr. Flaherty asked the panelists to explain adjustments their organizations have made in response to the pandemic, discuss accomplishments, and speculate on future challenges and priorities.
Trial, administrative, and patient-care modifications
COVID-19 put some cancer trials on hold. For others, the pandemic forced sponsors and study chairs to reduce trial complexity and identify nonessential aspects of the studies, according to panelist José Baselga, MD, PhD, of AstraZeneca.
Specifically, exploratory objectives were subjugated to patient safety and a focus on the primary endpoints of each trial.
Once the critical data were identified, study chairs were asked to determine whether data could be obtained through technologies that could substitute for face-to-face contact between patients and staff – for example, patient-reported outcome tools and at-home digital monitoring.
Modifications prompted by the pandemic include the following:
- On-site auditing was suspended.
- Oral investigational agents were shipped directly to patients.
- “Remote” informed consent (telephone or video consenting) was permitted.
- Local providers could perform study-related services, with oversight by the research site.
- Minor deviations from the written protocols were allowed, provided the deviations did not affect patient care or data integrity.
“Obviously, the pandemic has been horrible, but what it has allowed us to do, as investigators in the clinical research landscape, … is to change our focus somewhat and realize, first and foremost, the patient is at the center of this,” Dr. LoRusso said.
Operational accomplishments and benefits
The pandemic caused a 40% decline in accrual to studies supported by the National Cancer Institute’s (NCI) Clinical Trials Network (NCTN) from mid-March to early April, according to James H. Doroshow, MD, of NCI.
However, after modifications to administrative and regulatory procedures, accrual to NCTN trials recovered to approximately 80% of prepandemic levels, Dr. Doroshow said.
The pandemic prompted investigators to leverage tools and technology they had not previously used frequently or at all, the panelists pointed out.
Investigators discovered perforce that telehealth could be used for almost all trial-related assessments. In lieu of physical examination, patients could send pictures of rashes and use electronic devices to monitor blood sugar values and vital signs.
Digital radiographic studies were performed at sites that were most convenient for patients, downloaded, and reinterpreted at the study institution. Visiting nurses and neighborhood laboratories enabled less-frequent in-person visits for assessments.
These adjustments have been particularly important for geographically and/or socioeconomically disadvantaged patients, the panelists said.
Overall, there was agreement among the panelists that shared values and trust among regulatory authorities, sponsors, investigators, and clinicians were impressive in their urgency, sincerity, and patient centricity.
“This pandemic … has forced us to think differently and be nimble and creative to our approach to maintaining our overriding goals while at the same time bringing these innovative therapies forward for patients with cancer and other serious and life-threatening diseases as quickly as possible,” said panelist Kristen M. Hege, MD, of Bristol-Myers Squibb.
In fact, Dr. Hege noted, some cancer-related therapies (e.g., BTK inhibitors, JAK inhibitors, and immunomodulatory agents) were “repurposed” rapidly and tested against COVID-related complications.
Streamlining trial regulatory processes
In addition to changing ongoing trials, the pandemic has affected how new research projects are launched.
One new study that came together quickly in response to the pandemic is the NCI COVID-19 in Cancer Patients Study (NCCAPS). NCCAPS is a natural history study with biospecimens and an imaging library. It was approved in just 5 weeks and is active in 650 sites, with “gangbusters” accrual, Dr. Doroshow said.
The rapidness of NCCAPS’ design and implementation should prompt the revision of previously accepted timelines for trial activation and lead to streamlined future processes.
Another project that was launched quickly in response to the pandemic is the COVID-19 evidence accelerator, according to Paul G. Kluetz, MD, of the Food and Drug Administration.
The COVID-19 evidence accelerator integrates real-world evidence into a database to provide investigators and health systems with the ability to gather information, design rapid turnaround queries, and share results. The evidence accelerator can provide study chairs with information that may have relevance to the safety of participants in clinical trials.
Future directions and challenges
The panelists agreed that pandemic-related modifications in processes will not only accelerate trial approval and activation but should facilitate higher study accrual, increase the diversity of protocol participants, and decrease the costs associated with clinical trial conduct.
With that in mind, the NCI is planning randomized clinical trials in which “process A” is compared with “process B,” Dr. Doroshow said. The goal is to determine which modifications are most likely to make trials available to patients without compromising data integrity or patient safety.
“How much less data do you need to have an outcome that will be similar?” Dr. Doroshow asked. “How many fewer visits, how many fewer tests, how much can you save? Physicians, clinical trialists, all of us respond to data, and if you get the same outcome at a third of the cost, then everybody benefits.”
Nonetheless, we will need to be vigilant for unintended vulnerabilities from well-intended efforts, according to Dr. Kluetz. Study chairs, sponsors, and regulatory agencies will need to be attentive to whether there are important differences in scan quality or interpretation, missing data that influence trial outcomes, and so on.
Dr. Hege pointed out that differences among data sources may be less important when treatments generate large effects but may be vitally important when the relative differences among treatments are small.
On a practical level, decentralizing clinical research may negatively impact the finances of tertiary care centers, which could threaten the required infrastructure for clinical trials, a few panelists noted.
The relative balance of NCI-, industry-, and investigator-initiated trials may require adjustment so that research income is adequate to maintain the costs associated with cancer clinical trials.
Shared goals and democratization
The pandemic has required all stakeholders in clinical research to rely on relationships of trust and shared goals, said Caroline Robert, MD, PhD, of Institut Gustave Roussy in Villejuif, France.
Dr. Kluetz summarized those goals as improving trial efficiencies, decreasing patient burden, decentralizing trials, and maintaining trial integrity.
A decentralized clinical trials operational model could lead to better generalizability of study outcomes, normalization of life for patients on studies, and lower costs of trial conduct. As such, decentralization would promote democratization.
Coupled with ongoing efforts to reduce eligibility criteria in cancer trials, the pandemic has brought operational solutions that should be perpetuated and has reminded us of the interlocking and mutually supportive relationships on which clinical research success depends.
Dr. Doroshow and Dr. Kluetz disclosed no conflicts of interest. All other panelists disclosed financial relationships, including employment, with a range of companies.
Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.
SOURCE: Flaherty KT et al. AACR: COVID-19 and Cancer, Regulatory and Operational Implications of Cancer Clinical Trial Changes During COVID-19.
The pandemic has taught researchers how to decentralize trials, which should not only improve patient satisfaction but increase trial accrual by providing access to typically underserved populations, Patricia M. LoRusso, DO, of Yale University, New Haven, Conn., said at the meeting.
Dr. LoRusso was one of six panelists who participated in a forum about changes to cancer trials that were prompted by the pandemic. The forum was moderated by Keith T. Flaherty, MD, of Massachusetts General Hospital in Boston.
Dr. Flaherty asked the panelists to explain adjustments their organizations have made in response to the pandemic, discuss accomplishments, and speculate on future challenges and priorities.
Trial, administrative, and patient-care modifications
COVID-19 put some cancer trials on hold. For others, the pandemic forced sponsors and study chairs to reduce trial complexity and identify nonessential aspects of the studies, according to panelist José Baselga, MD, PhD, of AstraZeneca.
Specifically, exploratory objectives were subjugated to patient safety and a focus on the primary endpoints of each trial.
Once the critical data were identified, study chairs were asked to determine whether data could be obtained through technologies that could substitute for face-to-face contact between patients and staff – for example, patient-reported outcome tools and at-home digital monitoring.
Modifications prompted by the pandemic include the following:
- On-site auditing was suspended.
- Oral investigational agents were shipped directly to patients.
- “Remote” informed consent (telephone or video consenting) was permitted.
- Local providers could perform study-related services, with oversight by the research site.
- Minor deviations from the written protocols were allowed, provided the deviations did not affect patient care or data integrity.
“Obviously, the pandemic has been horrible, but what it has allowed us to do, as investigators in the clinical research landscape, … is to change our focus somewhat and realize, first and foremost, the patient is at the center of this,” Dr. LoRusso said.
Operational accomplishments and benefits
The pandemic caused a 40% decline in accrual to studies supported by the National Cancer Institute’s (NCI) Clinical Trials Network (NCTN) from mid-March to early April, according to James H. Doroshow, MD, of NCI.
However, after modifications to administrative and regulatory procedures, accrual to NCTN trials recovered to approximately 80% of prepandemic levels, Dr. Doroshow said.
The pandemic prompted investigators to leverage tools and technology they had not previously used frequently or at all, the panelists pointed out.
Investigators discovered perforce that telehealth could be used for almost all trial-related assessments. In lieu of physical examination, patients could send pictures of rashes and use electronic devices to monitor blood sugar values and vital signs.
Digital radiographic studies were performed at sites that were most convenient for patients, downloaded, and reinterpreted at the study institution. Visiting nurses and neighborhood laboratories enabled less-frequent in-person visits for assessments.
These adjustments have been particularly important for geographically and/or socioeconomically disadvantaged patients, the panelists said.
Overall, there was agreement among the panelists that shared values and trust among regulatory authorities, sponsors, investigators, and clinicians were impressive in their urgency, sincerity, and patient centricity.
“This pandemic … has forced us to think differently and be nimble and creative to our approach to maintaining our overriding goals while at the same time bringing these innovative therapies forward for patients with cancer and other serious and life-threatening diseases as quickly as possible,” said panelist Kristen M. Hege, MD, of Bristol-Myers Squibb.
In fact, Dr. Hege noted, some cancer-related therapies (e.g., BTK inhibitors, JAK inhibitors, and immunomodulatory agents) were “repurposed” rapidly and tested against COVID-related complications.
Streamlining trial regulatory processes
In addition to changing ongoing trials, the pandemic has affected how new research projects are launched.
One new study that came together quickly in response to the pandemic is the NCI COVID-19 in Cancer Patients Study (NCCAPS). NCCAPS is a natural history study with biospecimens and an imaging library. It was approved in just 5 weeks and is active in 650 sites, with “gangbusters” accrual, Dr. Doroshow said.
The rapidness of NCCAPS’ design and implementation should prompt the revision of previously accepted timelines for trial activation and lead to streamlined future processes.
Another project that was launched quickly in response to the pandemic is the COVID-19 evidence accelerator, according to Paul G. Kluetz, MD, of the Food and Drug Administration.
The COVID-19 evidence accelerator integrates real-world evidence into a database to provide investigators and health systems with the ability to gather information, design rapid turnaround queries, and share results. The evidence accelerator can provide study chairs with information that may have relevance to the safety of participants in clinical trials.
Future directions and challenges
The panelists agreed that pandemic-related modifications in processes will not only accelerate trial approval and activation but should facilitate higher study accrual, increase the diversity of protocol participants, and decrease the costs associated with clinical trial conduct.
With that in mind, the NCI is planning randomized clinical trials in which “process A” is compared with “process B,” Dr. Doroshow said. The goal is to determine which modifications are most likely to make trials available to patients without compromising data integrity or patient safety.
“How much less data do you need to have an outcome that will be similar?” Dr. Doroshow asked. “How many fewer visits, how many fewer tests, how much can you save? Physicians, clinical trialists, all of us respond to data, and if you get the same outcome at a third of the cost, then everybody benefits.”
Nonetheless, we will need to be vigilant for unintended vulnerabilities from well-intended efforts, according to Dr. Kluetz. Study chairs, sponsors, and regulatory agencies will need to be attentive to whether there are important differences in scan quality or interpretation, missing data that influence trial outcomes, and so on.
Dr. Hege pointed out that differences among data sources may be less important when treatments generate large effects but may be vitally important when the relative differences among treatments are small.
On a practical level, decentralizing clinical research may negatively impact the finances of tertiary care centers, which could threaten the required infrastructure for clinical trials, a few panelists noted.
The relative balance of NCI-, industry-, and investigator-initiated trials may require adjustment so that research income is adequate to maintain the costs associated with cancer clinical trials.
Shared goals and democratization
The pandemic has required all stakeholders in clinical research to rely on relationships of trust and shared goals, said Caroline Robert, MD, PhD, of Institut Gustave Roussy in Villejuif, France.
Dr. Kluetz summarized those goals as improving trial efficiencies, decreasing patient burden, decentralizing trials, and maintaining trial integrity.
A decentralized clinical trials operational model could lead to better generalizability of study outcomes, normalization of life for patients on studies, and lower costs of trial conduct. As such, decentralization would promote democratization.
Coupled with ongoing efforts to reduce eligibility criteria in cancer trials, the pandemic has brought operational solutions that should be perpetuated and has reminded us of the interlocking and mutually supportive relationships on which clinical research success depends.
Dr. Doroshow and Dr. Kluetz disclosed no conflicts of interest. All other panelists disclosed financial relationships, including employment, with a range of companies.
Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.
SOURCE: Flaherty KT et al. AACR: COVID-19 and Cancer, Regulatory and Operational Implications of Cancer Clinical Trial Changes During COVID-19.
FROM AACR: COVID-19 and Cancer
The march of immunotherapy continues at ESMO 2020
The use of immunotherapy for upper gastrointestinal tumors and renal cancer, ALK- and EGFR-targeted agents in non–small cell lung cancer (NSCLC), and the next step in personalized prostate cancer management will all be subjects of headlining presentations at the ESMO Virtual Congress 2020.
The conference will, like so many other major events, be held online this year because of the COVID-19 pandemic.
John B. Haanen, PhD, ESMO 2020 scientific chair, who is from the Netherlands Cancer Institute, Amsterdam, the Netherlands, told Medscape Medical News that, because the congress is being held online this year, fewer abstracts were submitted; nevertheless, “We were very happy to see ... that the quality was very good.”
The number of submissions was not the only problem the organizing committee had to face in transforming the ESMO Congress into a virtual meeting.
They were unable to fit the scientific and educational programs together and so have had to split them over two consecutive weekends. Moreover, many of the sessions were highly interactive and needed to be either adapted or omitted.
“So the program is somewhat different,” Haanen said. He noted that “the presentations were also made shorter, especially on the educational sessions, because...we can’t expect people to sit behind screens for hours listening to long presentations.”
He added: “That was out of the question.”
Haanen is nevertheless hopeful that the virtual meeting will be “very exciting.”
Solange Peters, MD, PhD, ESMO president, who is also affiliated with the Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, said in a press conference that it was a “sacrifice” to move ESMO 2020 online and that “there were very sad moments” when deciding on the content.
However, there were some benefits from the change.
She said that all of the ESMO meetings this year have seen “huge” increases in the number of attendees and the geographical span or reach of each of the conferences.
“So suddenly you also realize that, what is one of the missions of ESMO being to convey education globally ... was probably better reached, better achieved with the virtual format,” she commented.
Presidential symposia
Turning to the program, Haanen first picked out the third presidential symposium, which will be held on Monday, September 21. This will focus entirely on upper gastrointestinal tumors in both the adjuvant and metastatic setting.
He said that in recent years, “very little progress has been made” in this area, with treatment mostly consisting of chemotherapy and chemoradiotherapy.
However, this year’s presentations will explore the addition of immunotherapy either to chemotherapy or as an adjuvant treatment following completion of standard-of-care treatment for local disease.
Haanen said that the results will be “very interesting ... and may change current practice,” something that “is very important for both doctors and their patients.”
On Saturday, September 19, the first presidential symposium will include two presentations on lung cancer that Haanen said will offer some “exciting new [results] that I am sure will change clinical practice.”
One will be on the CROWN phase 3 trial comparing lorlatinib and crizotinib in the first-line treatment of patients with advanced ALK-positive NSCLC.
The other will present results on central nervous system disease recurrence from the ADAURA phase 3 trial of osimertinib adjuvant therapy in patients with resected EGFR-mutated NSCLC.
The same session will also see new data in advanced renal cell carcinoma from CheckMate 9ER, in which the c-Met and VEGFR2 inhibitor cabozantinib (Cabometyx) was combined with nivolumab (Opdivo) and compared to sunitinib (Sutent) in untreated patients.
“Last year, there were already some exciting results of the combination of axitinib [Inlyta], either with pembrolizumab [Keytruda] or with avelumab [Bavencio]...in the first-line setting in metastatic clear cell renal cell cancer,” Hannen said.
“Clearly there was a survival advantage over the standard of care, sunitinib,” he added.
This year, not only will efficacy data from CheckMate 9ER be presented but also quality-of-life results.
“That’s very important, because what everybody is afraid of is that, by adding drugs, you always get more impact on the quality of life, but you will see that the quality-of-life results are very exciting,” he said.
The second presidential symposium will feature studies on prostate cancer, notably the phase 3 IPATential150 trial of abiraterone (Zytiga) plus either ipatasertib or placebo in metastatic castration-resistant prostate cancer.
Ipatasertib targets Akt, and Haanen said that “by adding it to, let’s say, standard-of-care treatment ... the question of course of will be, Does that have a better outcome?”
He believes the results will be a “very nice illustration” that prostate cancer management is heading in the direction of personalized treatment.
Alongside the presidential symposia, there will be a number of proffered paper sessions on the latest results in all aspects of oncology, including results from the ASCENT trial in triple-negative breast cancer, as well as a dedicated COVID-19 track.
Haanen said that the ESMO Virtual Congress 2020, coming after the AACR and ASCO annual meetings, has the “advantage” of being able to present the latest outcomes of patients treated with chemotherapy and immunotherapy against the backdrop of the pandemic.
This will include a study from the ESMO Resilience Task Force on the impact of COVID-19 on oncology professionals both in terms of their personal distress and burnout and their job performance.
“I think that is very important,” Haanen said, “especially because the whole thing with COVID-19 is not yet over, and everybody is preparing for a second wave in the fall and winter.
“It may help us give us clues on how we can protect ourselves or each other to prevent burnout or other problems that we as healthcare caregivers face in this difficult period.”
Next year
For next year, Peters remains hopeful that the ESMO 2021 meeting will take place as planned in Paris.
She anticipates that, indeed, ESMO meetings will be able to take place from spring next year.
This will depend on a vaccine for COVID-19 becoming widely available, although oncologists in some countries may still not be able to travel.
This means “starting probably with hybrid formats, with some of the faculty being on site and some not, [and] the same thing for the attendees,” Peters said.
She suggested that, for ESMO Congress 2021 to work as an on-site meeting, it will require at least half or two-thirds of the originally anticipated number of attendees.
“I hope that Paris next year will happen,” Peters said, adding that it “will probably happen with less attendees – that’s fine, but [still] with a large number of faculty and attendees.”
The commentators have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
The use of immunotherapy for upper gastrointestinal tumors and renal cancer, ALK- and EGFR-targeted agents in non–small cell lung cancer (NSCLC), and the next step in personalized prostate cancer management will all be subjects of headlining presentations at the ESMO Virtual Congress 2020.
The conference will, like so many other major events, be held online this year because of the COVID-19 pandemic.
John B. Haanen, PhD, ESMO 2020 scientific chair, who is from the Netherlands Cancer Institute, Amsterdam, the Netherlands, told Medscape Medical News that, because the congress is being held online this year, fewer abstracts were submitted; nevertheless, “We were very happy to see ... that the quality was very good.”
The number of submissions was not the only problem the organizing committee had to face in transforming the ESMO Congress into a virtual meeting.
They were unable to fit the scientific and educational programs together and so have had to split them over two consecutive weekends. Moreover, many of the sessions were highly interactive and needed to be either adapted or omitted.
“So the program is somewhat different,” Haanen said. He noted that “the presentations were also made shorter, especially on the educational sessions, because...we can’t expect people to sit behind screens for hours listening to long presentations.”
He added: “That was out of the question.”
Haanen is nevertheless hopeful that the virtual meeting will be “very exciting.”
Solange Peters, MD, PhD, ESMO president, who is also affiliated with the Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, said in a press conference that it was a “sacrifice” to move ESMO 2020 online and that “there were very sad moments” when deciding on the content.
However, there were some benefits from the change.
She said that all of the ESMO meetings this year have seen “huge” increases in the number of attendees and the geographical span or reach of each of the conferences.
“So suddenly you also realize that, what is one of the missions of ESMO being to convey education globally ... was probably better reached, better achieved with the virtual format,” she commented.
Presidential symposia
Turning to the program, Haanen first picked out the third presidential symposium, which will be held on Monday, September 21. This will focus entirely on upper gastrointestinal tumors in both the adjuvant and metastatic setting.
He said that in recent years, “very little progress has been made” in this area, with treatment mostly consisting of chemotherapy and chemoradiotherapy.
However, this year’s presentations will explore the addition of immunotherapy either to chemotherapy or as an adjuvant treatment following completion of standard-of-care treatment for local disease.
Haanen said that the results will be “very interesting ... and may change current practice,” something that “is very important for both doctors and their patients.”
On Saturday, September 19, the first presidential symposium will include two presentations on lung cancer that Haanen said will offer some “exciting new [results] that I am sure will change clinical practice.”
One will be on the CROWN phase 3 trial comparing lorlatinib and crizotinib in the first-line treatment of patients with advanced ALK-positive NSCLC.
The other will present results on central nervous system disease recurrence from the ADAURA phase 3 trial of osimertinib adjuvant therapy in patients with resected EGFR-mutated NSCLC.
The same session will also see new data in advanced renal cell carcinoma from CheckMate 9ER, in which the c-Met and VEGFR2 inhibitor cabozantinib (Cabometyx) was combined with nivolumab (Opdivo) and compared to sunitinib (Sutent) in untreated patients.
“Last year, there were already some exciting results of the combination of axitinib [Inlyta], either with pembrolizumab [Keytruda] or with avelumab [Bavencio]...in the first-line setting in metastatic clear cell renal cell cancer,” Hannen said.
“Clearly there was a survival advantage over the standard of care, sunitinib,” he added.
This year, not only will efficacy data from CheckMate 9ER be presented but also quality-of-life results.
“That’s very important, because what everybody is afraid of is that, by adding drugs, you always get more impact on the quality of life, but you will see that the quality-of-life results are very exciting,” he said.
The second presidential symposium will feature studies on prostate cancer, notably the phase 3 IPATential150 trial of abiraterone (Zytiga) plus either ipatasertib or placebo in metastatic castration-resistant prostate cancer.
Ipatasertib targets Akt, and Haanen said that “by adding it to, let’s say, standard-of-care treatment ... the question of course of will be, Does that have a better outcome?”
He believes the results will be a “very nice illustration” that prostate cancer management is heading in the direction of personalized treatment.
Alongside the presidential symposia, there will be a number of proffered paper sessions on the latest results in all aspects of oncology, including results from the ASCENT trial in triple-negative breast cancer, as well as a dedicated COVID-19 track.
Haanen said that the ESMO Virtual Congress 2020, coming after the AACR and ASCO annual meetings, has the “advantage” of being able to present the latest outcomes of patients treated with chemotherapy and immunotherapy against the backdrop of the pandemic.
This will include a study from the ESMO Resilience Task Force on the impact of COVID-19 on oncology professionals both in terms of their personal distress and burnout and their job performance.
“I think that is very important,” Haanen said, “especially because the whole thing with COVID-19 is not yet over, and everybody is preparing for a second wave in the fall and winter.
“It may help us give us clues on how we can protect ourselves or each other to prevent burnout or other problems that we as healthcare caregivers face in this difficult period.”
Next year
For next year, Peters remains hopeful that the ESMO 2021 meeting will take place as planned in Paris.
She anticipates that, indeed, ESMO meetings will be able to take place from spring next year.
This will depend on a vaccine for COVID-19 becoming widely available, although oncologists in some countries may still not be able to travel.
This means “starting probably with hybrid formats, with some of the faculty being on site and some not, [and] the same thing for the attendees,” Peters said.
She suggested that, for ESMO Congress 2021 to work as an on-site meeting, it will require at least half or two-thirds of the originally anticipated number of attendees.
“I hope that Paris next year will happen,” Peters said, adding that it “will probably happen with less attendees – that’s fine, but [still] with a large number of faculty and attendees.”
The commentators have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
The use of immunotherapy for upper gastrointestinal tumors and renal cancer, ALK- and EGFR-targeted agents in non–small cell lung cancer (NSCLC), and the next step in personalized prostate cancer management will all be subjects of headlining presentations at the ESMO Virtual Congress 2020.
The conference will, like so many other major events, be held online this year because of the COVID-19 pandemic.
John B. Haanen, PhD, ESMO 2020 scientific chair, who is from the Netherlands Cancer Institute, Amsterdam, the Netherlands, told Medscape Medical News that, because the congress is being held online this year, fewer abstracts were submitted; nevertheless, “We were very happy to see ... that the quality was very good.”
The number of submissions was not the only problem the organizing committee had to face in transforming the ESMO Congress into a virtual meeting.
They were unable to fit the scientific and educational programs together and so have had to split them over two consecutive weekends. Moreover, many of the sessions were highly interactive and needed to be either adapted or omitted.
“So the program is somewhat different,” Haanen said. He noted that “the presentations were also made shorter, especially on the educational sessions, because...we can’t expect people to sit behind screens for hours listening to long presentations.”
He added: “That was out of the question.”
Haanen is nevertheless hopeful that the virtual meeting will be “very exciting.”
Solange Peters, MD, PhD, ESMO president, who is also affiliated with the Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, said in a press conference that it was a “sacrifice” to move ESMO 2020 online and that “there were very sad moments” when deciding on the content.
However, there were some benefits from the change.
She said that all of the ESMO meetings this year have seen “huge” increases in the number of attendees and the geographical span or reach of each of the conferences.
“So suddenly you also realize that, what is one of the missions of ESMO being to convey education globally ... was probably better reached, better achieved with the virtual format,” she commented.
Presidential symposia
Turning to the program, Haanen first picked out the third presidential symposium, which will be held on Monday, September 21. This will focus entirely on upper gastrointestinal tumors in both the adjuvant and metastatic setting.
He said that in recent years, “very little progress has been made” in this area, with treatment mostly consisting of chemotherapy and chemoradiotherapy.
However, this year’s presentations will explore the addition of immunotherapy either to chemotherapy or as an adjuvant treatment following completion of standard-of-care treatment for local disease.
Haanen said that the results will be “very interesting ... and may change current practice,” something that “is very important for both doctors and their patients.”
On Saturday, September 19, the first presidential symposium will include two presentations on lung cancer that Haanen said will offer some “exciting new [results] that I am sure will change clinical practice.”
One will be on the CROWN phase 3 trial comparing lorlatinib and crizotinib in the first-line treatment of patients with advanced ALK-positive NSCLC.
The other will present results on central nervous system disease recurrence from the ADAURA phase 3 trial of osimertinib adjuvant therapy in patients with resected EGFR-mutated NSCLC.
The same session will also see new data in advanced renal cell carcinoma from CheckMate 9ER, in which the c-Met and VEGFR2 inhibitor cabozantinib (Cabometyx) was combined with nivolumab (Opdivo) and compared to sunitinib (Sutent) in untreated patients.
“Last year, there were already some exciting results of the combination of axitinib [Inlyta], either with pembrolizumab [Keytruda] or with avelumab [Bavencio]...in the first-line setting in metastatic clear cell renal cell cancer,” Hannen said.
“Clearly there was a survival advantage over the standard of care, sunitinib,” he added.
This year, not only will efficacy data from CheckMate 9ER be presented but also quality-of-life results.
“That’s very important, because what everybody is afraid of is that, by adding drugs, you always get more impact on the quality of life, but you will see that the quality-of-life results are very exciting,” he said.
The second presidential symposium will feature studies on prostate cancer, notably the phase 3 IPATential150 trial of abiraterone (Zytiga) plus either ipatasertib or placebo in metastatic castration-resistant prostate cancer.
Ipatasertib targets Akt, and Haanen said that “by adding it to, let’s say, standard-of-care treatment ... the question of course of will be, Does that have a better outcome?”
He believes the results will be a “very nice illustration” that prostate cancer management is heading in the direction of personalized treatment.
Alongside the presidential symposia, there will be a number of proffered paper sessions on the latest results in all aspects of oncology, including results from the ASCENT trial in triple-negative breast cancer, as well as a dedicated COVID-19 track.
Haanen said that the ESMO Virtual Congress 2020, coming after the AACR and ASCO annual meetings, has the “advantage” of being able to present the latest outcomes of patients treated with chemotherapy and immunotherapy against the backdrop of the pandemic.
This will include a study from the ESMO Resilience Task Force on the impact of COVID-19 on oncology professionals both in terms of their personal distress and burnout and their job performance.
“I think that is very important,” Haanen said, “especially because the whole thing with COVID-19 is not yet over, and everybody is preparing for a second wave in the fall and winter.
“It may help us give us clues on how we can protect ourselves or each other to prevent burnout or other problems that we as healthcare caregivers face in this difficult period.”
Next year
For next year, Peters remains hopeful that the ESMO 2021 meeting will take place as planned in Paris.
She anticipates that, indeed, ESMO meetings will be able to take place from spring next year.
This will depend on a vaccine for COVID-19 becoming widely available, although oncologists in some countries may still not be able to travel.
This means “starting probably with hybrid formats, with some of the faculty being on site and some not, [and] the same thing for the attendees,” Peters said.
She suggested that, for ESMO Congress 2021 to work as an on-site meeting, it will require at least half or two-thirds of the originally anticipated number of attendees.
“I hope that Paris next year will happen,” Peters said, adding that it “will probably happen with less attendees – that’s fine, but [still] with a large number of faculty and attendees.”
The commentators have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
FROM ESMO 2020
Pralsetinib: Second drug for RET+ NSCLC approved in U.S.
A second drug is now available in the United States for use in the treatment of patients with metastatic non–small cell lung cancer (NSCLC) that tests positive for rearranged during transfection (RET) fusions.
The new drug is pralsetinib (Gavreto). The Food and Drug Administration granted it an accelerated approval for this indication on the basis of response rate data. Continued approval for this indication depends on clinical benefit in a confirmatory trial.
Pralsetinib joins selpercatinib (Retevmo), which was approved in the United States in May 2020 as the first RET-targeted therapy. Selpercatinib is also indicated for use in RET+ NSCLC and was approved for use in RET+ medullary thyroid cancer and RET+ thyroid cancer.
Pralsetinib is still awaiting approval for these thyroid cancer indications.
Both drugs are taken orally; pralsetinib is taken once daily, and selpercatinib is taken twice daily.
For both drugs, before treatment is initiated, laboratory testing is needed to show that a RET gene alteration is present in the tumor.
RET fusions are found in approximately 1%-2% of patients with NSCLC.
They are the latest of a number of tumor-specific gene alterations found in NSCLC that are targeted with an approved drug.
“Targeted therapies have dramatically improved care for patients with non–small cell lung cancer driven by oncogenes, including EGFR and ALK, and the approval of the selective RET inhibitor pralsetinib, or Gavreto, marks another milestone in a paradigm shift toward precision medicine,” Vivek Subbiah, MD, of the University of Texas MD Anderson Cancer Center, Houston, said in a press release.
Dr. Subbiah was an investigator of the phase 1/2 clinical trial known as ARROW, which provided the data on which the accelerated approval was based. In this trial, patients with RET+ NSCLC were found by testing with next-generation sequencing, FISH (fluorescence in situ hybridization), or other methods.
The ARROW trial involved one cohort of 87 patients who had previously been treated with platinum-based chemotherapy. In these patients, the overall response rate (ORR) was 57%, the complete response (CR) rate was 5.7%, and the median duration of response (DOR) was not estimable, according to the manufacturer, Blueprint Medicines.
The trial also involved 27 treatment-naive patients who were ineligible for platinum-based chemotherapy per the study protocol. In this group, the ORR was 70%, and the CR rate was 11%. The median DOR was 9.0 months.
“Patients treated with [pralsetinib] had durable clinical responses, with a subset achieving complete responses characterized by the resolution of all target lesions, an uncommon outcome in metastatic lung cancer,” Dr. Subbiah commented.
“We observed this activity with or without prior therapy and regardless of RET fusion partner or the presence of brain metastases. This approval represents an important advance with the potential to change standards of care for patients with RET fusion-positive NSCLC, who have historically had limited treatment options,” Dr. Subbiah added.
Product information for pralsetinib has warnings and precautions of interstitial lung disease/pneumonitis, hypertension, hepatotoxicity, hemorrhagic events, risk for impaired wound healing, and risk for embryo-fetal toxicity.
This article first appeared on Medscape.com.
A second drug is now available in the United States for use in the treatment of patients with metastatic non–small cell lung cancer (NSCLC) that tests positive for rearranged during transfection (RET) fusions.
The new drug is pralsetinib (Gavreto). The Food and Drug Administration granted it an accelerated approval for this indication on the basis of response rate data. Continued approval for this indication depends on clinical benefit in a confirmatory trial.
Pralsetinib joins selpercatinib (Retevmo), which was approved in the United States in May 2020 as the first RET-targeted therapy. Selpercatinib is also indicated for use in RET+ NSCLC and was approved for use in RET+ medullary thyroid cancer and RET+ thyroid cancer.
Pralsetinib is still awaiting approval for these thyroid cancer indications.
Both drugs are taken orally; pralsetinib is taken once daily, and selpercatinib is taken twice daily.
For both drugs, before treatment is initiated, laboratory testing is needed to show that a RET gene alteration is present in the tumor.
RET fusions are found in approximately 1%-2% of patients with NSCLC.
They are the latest of a number of tumor-specific gene alterations found in NSCLC that are targeted with an approved drug.
“Targeted therapies have dramatically improved care for patients with non–small cell lung cancer driven by oncogenes, including EGFR and ALK, and the approval of the selective RET inhibitor pralsetinib, or Gavreto, marks another milestone in a paradigm shift toward precision medicine,” Vivek Subbiah, MD, of the University of Texas MD Anderson Cancer Center, Houston, said in a press release.
Dr. Subbiah was an investigator of the phase 1/2 clinical trial known as ARROW, which provided the data on which the accelerated approval was based. In this trial, patients with RET+ NSCLC were found by testing with next-generation sequencing, FISH (fluorescence in situ hybridization), or other methods.
The ARROW trial involved one cohort of 87 patients who had previously been treated with platinum-based chemotherapy. In these patients, the overall response rate (ORR) was 57%, the complete response (CR) rate was 5.7%, and the median duration of response (DOR) was not estimable, according to the manufacturer, Blueprint Medicines.
The trial also involved 27 treatment-naive patients who were ineligible for platinum-based chemotherapy per the study protocol. In this group, the ORR was 70%, and the CR rate was 11%. The median DOR was 9.0 months.
“Patients treated with [pralsetinib] had durable clinical responses, with a subset achieving complete responses characterized by the resolution of all target lesions, an uncommon outcome in metastatic lung cancer,” Dr. Subbiah commented.
“We observed this activity with or without prior therapy and regardless of RET fusion partner or the presence of brain metastases. This approval represents an important advance with the potential to change standards of care for patients with RET fusion-positive NSCLC, who have historically had limited treatment options,” Dr. Subbiah added.
Product information for pralsetinib has warnings and precautions of interstitial lung disease/pneumonitis, hypertension, hepatotoxicity, hemorrhagic events, risk for impaired wound healing, and risk for embryo-fetal toxicity.
This article first appeared on Medscape.com.
A second drug is now available in the United States for use in the treatment of patients with metastatic non–small cell lung cancer (NSCLC) that tests positive for rearranged during transfection (RET) fusions.
The new drug is pralsetinib (Gavreto). The Food and Drug Administration granted it an accelerated approval for this indication on the basis of response rate data. Continued approval for this indication depends on clinical benefit in a confirmatory trial.
Pralsetinib joins selpercatinib (Retevmo), which was approved in the United States in May 2020 as the first RET-targeted therapy. Selpercatinib is also indicated for use in RET+ NSCLC and was approved for use in RET+ medullary thyroid cancer and RET+ thyroid cancer.
Pralsetinib is still awaiting approval for these thyroid cancer indications.
Both drugs are taken orally; pralsetinib is taken once daily, and selpercatinib is taken twice daily.
For both drugs, before treatment is initiated, laboratory testing is needed to show that a RET gene alteration is present in the tumor.
RET fusions are found in approximately 1%-2% of patients with NSCLC.
They are the latest of a number of tumor-specific gene alterations found in NSCLC that are targeted with an approved drug.
“Targeted therapies have dramatically improved care for patients with non–small cell lung cancer driven by oncogenes, including EGFR and ALK, and the approval of the selective RET inhibitor pralsetinib, or Gavreto, marks another milestone in a paradigm shift toward precision medicine,” Vivek Subbiah, MD, of the University of Texas MD Anderson Cancer Center, Houston, said in a press release.
Dr. Subbiah was an investigator of the phase 1/2 clinical trial known as ARROW, which provided the data on which the accelerated approval was based. In this trial, patients with RET+ NSCLC were found by testing with next-generation sequencing, FISH (fluorescence in situ hybridization), or other methods.
The ARROW trial involved one cohort of 87 patients who had previously been treated with platinum-based chemotherapy. In these patients, the overall response rate (ORR) was 57%, the complete response (CR) rate was 5.7%, and the median duration of response (DOR) was not estimable, according to the manufacturer, Blueprint Medicines.
The trial also involved 27 treatment-naive patients who were ineligible for platinum-based chemotherapy per the study protocol. In this group, the ORR was 70%, and the CR rate was 11%. The median DOR was 9.0 months.
“Patients treated with [pralsetinib] had durable clinical responses, with a subset achieving complete responses characterized by the resolution of all target lesions, an uncommon outcome in metastatic lung cancer,” Dr. Subbiah commented.
“We observed this activity with or without prior therapy and regardless of RET fusion partner or the presence of brain metastases. This approval represents an important advance with the potential to change standards of care for patients with RET fusion-positive NSCLC, who have historically had limited treatment options,” Dr. Subbiah added.
Product information for pralsetinib has warnings and precautions of interstitial lung disease/pneumonitis, hypertension, hepatotoxicity, hemorrhagic events, risk for impaired wound healing, and risk for embryo-fetal toxicity.
This article first appeared on Medscape.com.
First drug for MET+ NSCLC shows high response rates
conclude investigators of the pivotal trial that led to the drug’s approval.
Responses were seen in all patients regardless of how many previous drugs they had been treated with, although responses were particularly pronounced among patients who were treatment naive.
Capmatinib and a companion assay received FDA approval in May 2020 for the treatment of adults with metastatic NSCLC harboring MET exon 14–skipping mutations.
These MET mutations occur in 3%-4% of NSCLC patients. MET amplifications occur in 1%-6% of NSCLC patients. They have been associated with poor response to chemotherapy and immunotherapy.
“Prior to this approval, there weren’t any approved therapies for this group of patients,” noted Edward Garon, MD, associate professor of hematology and oncology at the University of California, Los Angeles, who led the pivotal trial.
“There are several drugs that have been used off label for MET exon 14 skipping mutations, but none with an indication for it,” he said in an interview.
Garon emphasized that capmatinib was particularly robust for patients who had not received prior therapy, although he added that it was also very effective for those who had been previously treated.
“The drug has been approved and it is available, and we have already written prescriptions for it at our clinic,” said Dr. Garon, “although, at our clinic, the majority of patients using it were part of the [pivotal] clinical trial.”
That trial is the phase 2 GEOMETRY mono-1 study. Results from the study were presented at a meeting earlier this year and have now been published in the New England Journal of Medicine.
It was conducted in a cohort of 364 patients with advanced NSCLC. Patients were stratified into five cohorts and two expansion cohorts, which were assigned according to MET status and previous lines of therapy. Across cohorts 1 through 5, a total of 97 patients had a MET exon 14–skipping mutation, and 210 had MET amplification. All patients were treated with capmatinib 400 mg twice daily.
Among patients with a MET exon 14 skipping mutation, an overall response was observed in 41% of previously treated patients and in 68% of those who had not previously been treated.
“That is a very high response rate, and clearly this drug is targeting this mutation,” said Fred Hirsch, MD, PhD, executive director, Center for Thoracic Oncology, Mount Sinai Health System, New York, who was approached for comment. “It’s very active, and you don’t get those responses with chemotherapy.”
The median duration of response was 9.7 months among previously treated patients and 12.6 months among those who were treatment naive. Median progression-free survival (PFS) was 5.4 months and 12.4 months, respectively.
In the cohort of patients with MET amplification, the overall response was 12% among those whose tumor tissue had a gene copy number of 6-9. The overall response rate was 9% among those with a gene copy number of 4 or 5, and it was 7% among those with a gene copy number of less than 4.
Median PFS was 2.7 months for patients whose tumor tissue had a gene copy number of 6-9 and in those with a gene copy number of 4 or 5. PFS rose to 3.6 months for patients with a gene copy number of less than 4.
The most frequently reported adverse events were peripheral edema (in 51%) and nausea (in 45%). These events were mostly of grade 1 or 2. Treatment-related serious adverse events occurred in 13% of patients. The incidence was lower in the groups with shorter duration of exposure. Treatment was discontinued in 11% of patients (consistent across cohorts) because of adverse events.
Dr. Hirsch commented that the results for patients with NSCLC and brain metastases were particularly noteworthy. “Brain metastases are, unfortunately, a common problem in patients with lung cancer,” he said. “Now, we have a drug that is effective for MET mutation and CNS involvement and can penetrate the blood-brain barrier, and this is a very encouraging situation.”
He pointed out that 7 of 13 patients with brain metastases responded to treatment with capmatinib. “Four patients have a complete response, and that is very encouraging,” said Dr. Hirsch. “This is clearly a deal-breaker in my opinion.”
The future is bright
Dr. Hirsch noted that the evidence supporting capmatinib is strong, even though a larger prospective study with a control group is lacking. “If we have a patient with this mutation, and knowing that there is a drug with a response rate of 68%, that is a good reason to try the drug up front. The data are sufficient that it should be offered to the patient, even without a control group.”
Capmatinib is the latest of many targeted drugs that have been launched in recent years, and several immunotherapies are also now available for treatment of this disease. These new therapies are making this a “very encouraging time in lung cancer,” Dr. Hirsch commented.
“We are seeing long-term survival, and, eventually, we may start seeing potential cures for some patients,” he said. “But at the very least, we are seeing very good long-term results with many of these targeted therapies, and we are continuing to learn more about resistant mechanisms. I can’t wait to see future in the field.”
The study was funded by Novartis Pharmaceuticals. Dr. Garon reports consulting or advisory roles with Dracen and research funding (institutional) from Merck, Genentech, AstraZeneca, Novartis, Lilly, Bristol-Myers Squibb, Mirati Therapeutics, Dynavax, Iovance Biotherapeutics, and Neon Therapeutics. His coauthors have disclosed numerous relationships with industry, as listed in the original article. Dr. Hirsch has disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
conclude investigators of the pivotal trial that led to the drug’s approval.
Responses were seen in all patients regardless of how many previous drugs they had been treated with, although responses were particularly pronounced among patients who were treatment naive.
Capmatinib and a companion assay received FDA approval in May 2020 for the treatment of adults with metastatic NSCLC harboring MET exon 14–skipping mutations.
These MET mutations occur in 3%-4% of NSCLC patients. MET amplifications occur in 1%-6% of NSCLC patients. They have been associated with poor response to chemotherapy and immunotherapy.
“Prior to this approval, there weren’t any approved therapies for this group of patients,” noted Edward Garon, MD, associate professor of hematology and oncology at the University of California, Los Angeles, who led the pivotal trial.
“There are several drugs that have been used off label for MET exon 14 skipping mutations, but none with an indication for it,” he said in an interview.
Garon emphasized that capmatinib was particularly robust for patients who had not received prior therapy, although he added that it was also very effective for those who had been previously treated.
“The drug has been approved and it is available, and we have already written prescriptions for it at our clinic,” said Dr. Garon, “although, at our clinic, the majority of patients using it were part of the [pivotal] clinical trial.”
That trial is the phase 2 GEOMETRY mono-1 study. Results from the study were presented at a meeting earlier this year and have now been published in the New England Journal of Medicine.
It was conducted in a cohort of 364 patients with advanced NSCLC. Patients were stratified into five cohorts and two expansion cohorts, which were assigned according to MET status and previous lines of therapy. Across cohorts 1 through 5, a total of 97 patients had a MET exon 14–skipping mutation, and 210 had MET amplification. All patients were treated with capmatinib 400 mg twice daily.
Among patients with a MET exon 14 skipping mutation, an overall response was observed in 41% of previously treated patients and in 68% of those who had not previously been treated.
“That is a very high response rate, and clearly this drug is targeting this mutation,” said Fred Hirsch, MD, PhD, executive director, Center for Thoracic Oncology, Mount Sinai Health System, New York, who was approached for comment. “It’s very active, and you don’t get those responses with chemotherapy.”
The median duration of response was 9.7 months among previously treated patients and 12.6 months among those who were treatment naive. Median progression-free survival (PFS) was 5.4 months and 12.4 months, respectively.
In the cohort of patients with MET amplification, the overall response was 12% among those whose tumor tissue had a gene copy number of 6-9. The overall response rate was 9% among those with a gene copy number of 4 or 5, and it was 7% among those with a gene copy number of less than 4.
Median PFS was 2.7 months for patients whose tumor tissue had a gene copy number of 6-9 and in those with a gene copy number of 4 or 5. PFS rose to 3.6 months for patients with a gene copy number of less than 4.
The most frequently reported adverse events were peripheral edema (in 51%) and nausea (in 45%). These events were mostly of grade 1 or 2. Treatment-related serious adverse events occurred in 13% of patients. The incidence was lower in the groups with shorter duration of exposure. Treatment was discontinued in 11% of patients (consistent across cohorts) because of adverse events.
Dr. Hirsch commented that the results for patients with NSCLC and brain metastases were particularly noteworthy. “Brain metastases are, unfortunately, a common problem in patients with lung cancer,” he said. “Now, we have a drug that is effective for MET mutation and CNS involvement and can penetrate the blood-brain barrier, and this is a very encouraging situation.”
He pointed out that 7 of 13 patients with brain metastases responded to treatment with capmatinib. “Four patients have a complete response, and that is very encouraging,” said Dr. Hirsch. “This is clearly a deal-breaker in my opinion.”
The future is bright
Dr. Hirsch noted that the evidence supporting capmatinib is strong, even though a larger prospective study with a control group is lacking. “If we have a patient with this mutation, and knowing that there is a drug with a response rate of 68%, that is a good reason to try the drug up front. The data are sufficient that it should be offered to the patient, even without a control group.”
Capmatinib is the latest of many targeted drugs that have been launched in recent years, and several immunotherapies are also now available for treatment of this disease. These new therapies are making this a “very encouraging time in lung cancer,” Dr. Hirsch commented.
“We are seeing long-term survival, and, eventually, we may start seeing potential cures for some patients,” he said. “But at the very least, we are seeing very good long-term results with many of these targeted therapies, and we are continuing to learn more about resistant mechanisms. I can’t wait to see future in the field.”
The study was funded by Novartis Pharmaceuticals. Dr. Garon reports consulting or advisory roles with Dracen and research funding (institutional) from Merck, Genentech, AstraZeneca, Novartis, Lilly, Bristol-Myers Squibb, Mirati Therapeutics, Dynavax, Iovance Biotherapeutics, and Neon Therapeutics. His coauthors have disclosed numerous relationships with industry, as listed in the original article. Dr. Hirsch has disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
conclude investigators of the pivotal trial that led to the drug’s approval.
Responses were seen in all patients regardless of how many previous drugs they had been treated with, although responses were particularly pronounced among patients who were treatment naive.
Capmatinib and a companion assay received FDA approval in May 2020 for the treatment of adults with metastatic NSCLC harboring MET exon 14–skipping mutations.
These MET mutations occur in 3%-4% of NSCLC patients. MET amplifications occur in 1%-6% of NSCLC patients. They have been associated with poor response to chemotherapy and immunotherapy.
“Prior to this approval, there weren’t any approved therapies for this group of patients,” noted Edward Garon, MD, associate professor of hematology and oncology at the University of California, Los Angeles, who led the pivotal trial.
“There are several drugs that have been used off label for MET exon 14 skipping mutations, but none with an indication for it,” he said in an interview.
Garon emphasized that capmatinib was particularly robust for patients who had not received prior therapy, although he added that it was also very effective for those who had been previously treated.
“The drug has been approved and it is available, and we have already written prescriptions for it at our clinic,” said Dr. Garon, “although, at our clinic, the majority of patients using it were part of the [pivotal] clinical trial.”
That trial is the phase 2 GEOMETRY mono-1 study. Results from the study were presented at a meeting earlier this year and have now been published in the New England Journal of Medicine.
It was conducted in a cohort of 364 patients with advanced NSCLC. Patients were stratified into five cohorts and two expansion cohorts, which were assigned according to MET status and previous lines of therapy. Across cohorts 1 through 5, a total of 97 patients had a MET exon 14–skipping mutation, and 210 had MET amplification. All patients were treated with capmatinib 400 mg twice daily.
Among patients with a MET exon 14 skipping mutation, an overall response was observed in 41% of previously treated patients and in 68% of those who had not previously been treated.
“That is a very high response rate, and clearly this drug is targeting this mutation,” said Fred Hirsch, MD, PhD, executive director, Center for Thoracic Oncology, Mount Sinai Health System, New York, who was approached for comment. “It’s very active, and you don’t get those responses with chemotherapy.”
The median duration of response was 9.7 months among previously treated patients and 12.6 months among those who were treatment naive. Median progression-free survival (PFS) was 5.4 months and 12.4 months, respectively.
In the cohort of patients with MET amplification, the overall response was 12% among those whose tumor tissue had a gene copy number of 6-9. The overall response rate was 9% among those with a gene copy number of 4 or 5, and it was 7% among those with a gene copy number of less than 4.
Median PFS was 2.7 months for patients whose tumor tissue had a gene copy number of 6-9 and in those with a gene copy number of 4 or 5. PFS rose to 3.6 months for patients with a gene copy number of less than 4.
The most frequently reported adverse events were peripheral edema (in 51%) and nausea (in 45%). These events were mostly of grade 1 or 2. Treatment-related serious adverse events occurred in 13% of patients. The incidence was lower in the groups with shorter duration of exposure. Treatment was discontinued in 11% of patients (consistent across cohorts) because of adverse events.
Dr. Hirsch commented that the results for patients with NSCLC and brain metastases were particularly noteworthy. “Brain metastases are, unfortunately, a common problem in patients with lung cancer,” he said. “Now, we have a drug that is effective for MET mutation and CNS involvement and can penetrate the blood-brain barrier, and this is a very encouraging situation.”
He pointed out that 7 of 13 patients with brain metastases responded to treatment with capmatinib. “Four patients have a complete response, and that is very encouraging,” said Dr. Hirsch. “This is clearly a deal-breaker in my opinion.”
The future is bright
Dr. Hirsch noted that the evidence supporting capmatinib is strong, even though a larger prospective study with a control group is lacking. “If we have a patient with this mutation, and knowing that there is a drug with a response rate of 68%, that is a good reason to try the drug up front. The data are sufficient that it should be offered to the patient, even without a control group.”
Capmatinib is the latest of many targeted drugs that have been launched in recent years, and several immunotherapies are also now available for treatment of this disease. These new therapies are making this a “very encouraging time in lung cancer,” Dr. Hirsch commented.
“We are seeing long-term survival, and, eventually, we may start seeing potential cures for some patients,” he said. “But at the very least, we are seeing very good long-term results with many of these targeted therapies, and we are continuing to learn more about resistant mechanisms. I can’t wait to see future in the field.”
The study was funded by Novartis Pharmaceuticals. Dr. Garon reports consulting or advisory roles with Dracen and research funding (institutional) from Merck, Genentech, AstraZeneca, Novartis, Lilly, Bristol-Myers Squibb, Mirati Therapeutics, Dynavax, Iovance Biotherapeutics, and Neon Therapeutics. His coauthors have disclosed numerous relationships with industry, as listed in the original article. Dr. Hirsch has disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
Hair dye and cancer study ‘offers some reassurance’
Findings limited to White women in United States
The largest study of its kind has found no positive association between personal use of permanent hair dye and the risk for most cancers and cancer mortality.
The findings come from the Nurses’ Health Study, an ongoing prospective cohort study of more than 117,000 women who have been followed for 36 years and who did not have cancer at baseline.
The findings were published online on September 2 in the BMJ.
The results “offer some reassurance against concerns that personal use of permanent hair dyes might be associated with increased cancer risk or mortality,” write the investigators, with first author Yin Zhang, PhD, of Harvard Medical School, Boston.
The findings, which are limited to White women in the United States, indicate correlation, not causation, the authors emphasize.
Nevertheless, the researchers found an increased risk for some cancers among hair dye users, especially with greater cumulative dose (200 or more uses during the study period). The risk was increased for basal cell carcinoma, breast cancer (specifically, estrogen receptor negative [ER–], progesterone receptor negative [PR–], and hormone receptor negative [ER–, PR–]), and ovarian cancer.
A British expert not involved in the study dismissed these findings. “The reported associations are very weak, and, given the number of associations reported in this manuscript, they are very likely to be chance findings,” commented Paul Pharoah, PhD, professor of cancer epidemiology at the University of Cambridge (England).
“For the cancers where an increase in risk is reported, the results are not compelling. Even if they were real findings, the associations may not be cause-and-effect, and, even if they were causal associations, the magnitude of the effects are so small that any risk would be trivial.
“In short, none of the findings reported in this manuscript suggest that women who use hair dye are putting themselves at increased risk of cancer,” he stated.
A U.S. researcher who has previously coauthored a study suggesting an association between hair dye and breast cancer agreed that the increases in risk reported in this current study are “small.” But they are “of interest,” especially for breast and ovarian cancer, said Alexandra White, PhD, of the National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, N.C.
Hair dyes include compounds that “are not just potential carcinogens but also act as endocrine disruptors,” she said in an interview.
“In both breast and ovarian cancer, we know that hormones play an important part in the etiology ... so it’s biologically plausible that you would see [these associations in the current study],” added Dr. White, who was approached for comment.
However, she added that, even with the “modest” 20%-28% increase in the relative risk for certain breast cancers linked to a heavy cumulative dose of dyes in the current study, “there doesn’t seem to be any strong association with any cancer type.”
But she also pointed out that the most outstanding risk association was among ER–/PR– breast cancers, which are the “most aggressive and difficult to treat,” and thus the new findings are “important.”
Dr. White is the lead author of a 2019 study that received a lot of media attention because it rang an alarm bell about hair dyes and breast cancer risk.
That study concluded that ever using permanent hair dye or hair straighteners was associated with a higher risk for breast cancer than never using them and that this higher risk was especially associated with Black women. However, the study participants were from the prospective Sister Study. The participants in that study had no history of breast cancer, but they each had at least one sister who did. This family history of breast cancer may represent selection bias.
With changes in the 1980s, even safer now?
The study of hair dyes and cancer has “major public health implications” because the use of hair dye is widespread, Dr. Zhang and colleagues write in their article. They estimate that 50% to 80% of women and 10% of men aged 40 years and older in the United States and Europe use hair dye.
Permanent hair dyes “pose the greatest potential concern,” they stated, adding that these account for approximately 80% of hair dyes used in the United States and Europe and an even higher percentage in Asia.
The International Agency for Research on Cancer classifies occupational exposure to hair dyes as probably carcinogenic, but the carcinogenicity resulting from personal use of hair dyes is not classifiable – thus, there is no warning about at-home usage.
Notably, there was “a huge and very important” change in hair dye ingredients in the 1980s after the Food and Drug Administration warned about some chemicals in permanent hair dyes and the cosmetic industry altered their formulas, lead author Dr. Zhang said.
However, the researchers could not analyze use before and after the changes because not enough women reported first use of permanent hair dye after 1980 (only 1890 of 117,200 participants).
“We could expect that the current ingredients should make it safer,” Dr. Zhang said.
Study details
The researchers report that ever-users of permanent hair dyes had no significant increases in risk for solid cancers (n = 20,805; hazard ratio, 0.98, 95% confidence interval, 0.96-1.01) or hematopoietic cancers overall (n = 1,807; HR, 1.00; 95% CI, 0.91-1.10) compared with nonusers.
Additionally, ever-users did not have an increased risk for most specific cancers or cancer-related death (n = 4,860; HR, 0.96; 95% CI, 0.91-1.02).
As noted above, there were some exceptions.
Basal cell carcinoma risk was slightly increased for ever-users (n = 22,560; HR, 1.05; 95% CI, 1.02-1.08). Cumulative dose (a calculation of duration and frequency) was positively associated with risk for ER– breast cancer, PR– breast cancer, ER–/PR– breast cancer, and ovarian cancer, with risk rising in accordance with the total amount of dye.
Notably, at a cumulative dose of ≥200 uses, there was a 20% increase in the relative risk for ER- breast cancer (n = 1521; HR, 1.20; 95% CI, 1.02-1.41; P value for trend, .03). At the same cumulative dose, there was a 28% increase in the relative risk for ER-/PR- breast cancer (n = 1287; HR, 1.28, 95% CI, 1.08-1.52; P value for trend, .006).
In addition, an increased risk for Hodgkin lymphoma was observed, but only for women with naturally dark hair (the calculation was based on 70 women, 24 of whom had dark hair).
In a press statement, senior author Eva Schernhammer, PhD, of Harvard and the Medical University of Vienna, said the results “justify further prospective validation.”
She also explained that there are many variables to consider in this research, including different populations and countries, different susceptibility genotypes, different exposure settings (personal use vs. occupational exposure), and different colors of the permanent hair dyes used (dark dyes vs. light dyes).
Geographic location is a particularly important variable, suggested the study authors.
They pointed out that Europe, but not the United States, banned some individual hair dye ingredients that were considered carcinogenic during both the 1980s and 2000s. One country has even tighter oversight: “The most restrictive regulation of hair dyes exists in Japan, where cosmetic products are considered equivalent to drugs.”
The study was funded by the Centers for Disease Control and Prevention and the National Institute for Occupational Safety and Health. The study authors and Dr. White have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
Findings limited to White women in United States
Findings limited to White women in United States
The largest study of its kind has found no positive association between personal use of permanent hair dye and the risk for most cancers and cancer mortality.
The findings come from the Nurses’ Health Study, an ongoing prospective cohort study of more than 117,000 women who have been followed for 36 years and who did not have cancer at baseline.
The findings were published online on September 2 in the BMJ.
The results “offer some reassurance against concerns that personal use of permanent hair dyes might be associated with increased cancer risk or mortality,” write the investigators, with first author Yin Zhang, PhD, of Harvard Medical School, Boston.
The findings, which are limited to White women in the United States, indicate correlation, not causation, the authors emphasize.
Nevertheless, the researchers found an increased risk for some cancers among hair dye users, especially with greater cumulative dose (200 or more uses during the study period). The risk was increased for basal cell carcinoma, breast cancer (specifically, estrogen receptor negative [ER–], progesterone receptor negative [PR–], and hormone receptor negative [ER–, PR–]), and ovarian cancer.
A British expert not involved in the study dismissed these findings. “The reported associations are very weak, and, given the number of associations reported in this manuscript, they are very likely to be chance findings,” commented Paul Pharoah, PhD, professor of cancer epidemiology at the University of Cambridge (England).
“For the cancers where an increase in risk is reported, the results are not compelling. Even if they were real findings, the associations may not be cause-and-effect, and, even if they were causal associations, the magnitude of the effects are so small that any risk would be trivial.
“In short, none of the findings reported in this manuscript suggest that women who use hair dye are putting themselves at increased risk of cancer,” he stated.
A U.S. researcher who has previously coauthored a study suggesting an association between hair dye and breast cancer agreed that the increases in risk reported in this current study are “small.” But they are “of interest,” especially for breast and ovarian cancer, said Alexandra White, PhD, of the National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, N.C.
Hair dyes include compounds that “are not just potential carcinogens but also act as endocrine disruptors,” she said in an interview.
“In both breast and ovarian cancer, we know that hormones play an important part in the etiology ... so it’s biologically plausible that you would see [these associations in the current study],” added Dr. White, who was approached for comment.
However, she added that, even with the “modest” 20%-28% increase in the relative risk for certain breast cancers linked to a heavy cumulative dose of dyes in the current study, “there doesn’t seem to be any strong association with any cancer type.”
But she also pointed out that the most outstanding risk association was among ER–/PR– breast cancers, which are the “most aggressive and difficult to treat,” and thus the new findings are “important.”
Dr. White is the lead author of a 2019 study that received a lot of media attention because it rang an alarm bell about hair dyes and breast cancer risk.
That study concluded that ever using permanent hair dye or hair straighteners was associated with a higher risk for breast cancer than never using them and that this higher risk was especially associated with Black women. However, the study participants were from the prospective Sister Study. The participants in that study had no history of breast cancer, but they each had at least one sister who did. This family history of breast cancer may represent selection bias.
With changes in the 1980s, even safer now?
The study of hair dyes and cancer has “major public health implications” because the use of hair dye is widespread, Dr. Zhang and colleagues write in their article. They estimate that 50% to 80% of women and 10% of men aged 40 years and older in the United States and Europe use hair dye.
Permanent hair dyes “pose the greatest potential concern,” they stated, adding that these account for approximately 80% of hair dyes used in the United States and Europe and an even higher percentage in Asia.
The International Agency for Research on Cancer classifies occupational exposure to hair dyes as probably carcinogenic, but the carcinogenicity resulting from personal use of hair dyes is not classifiable – thus, there is no warning about at-home usage.
Notably, there was “a huge and very important” change in hair dye ingredients in the 1980s after the Food and Drug Administration warned about some chemicals in permanent hair dyes and the cosmetic industry altered their formulas, lead author Dr. Zhang said.
However, the researchers could not analyze use before and after the changes because not enough women reported first use of permanent hair dye after 1980 (only 1890 of 117,200 participants).
“We could expect that the current ingredients should make it safer,” Dr. Zhang said.
Study details
The researchers report that ever-users of permanent hair dyes had no significant increases in risk for solid cancers (n = 20,805; hazard ratio, 0.98, 95% confidence interval, 0.96-1.01) or hematopoietic cancers overall (n = 1,807; HR, 1.00; 95% CI, 0.91-1.10) compared with nonusers.
Additionally, ever-users did not have an increased risk for most specific cancers or cancer-related death (n = 4,860; HR, 0.96; 95% CI, 0.91-1.02).
As noted above, there were some exceptions.
Basal cell carcinoma risk was slightly increased for ever-users (n = 22,560; HR, 1.05; 95% CI, 1.02-1.08). Cumulative dose (a calculation of duration and frequency) was positively associated with risk for ER– breast cancer, PR– breast cancer, ER–/PR– breast cancer, and ovarian cancer, with risk rising in accordance with the total amount of dye.
Notably, at a cumulative dose of ≥200 uses, there was a 20% increase in the relative risk for ER- breast cancer (n = 1521; HR, 1.20; 95% CI, 1.02-1.41; P value for trend, .03). At the same cumulative dose, there was a 28% increase in the relative risk for ER-/PR- breast cancer (n = 1287; HR, 1.28, 95% CI, 1.08-1.52; P value for trend, .006).
In addition, an increased risk for Hodgkin lymphoma was observed, but only for women with naturally dark hair (the calculation was based on 70 women, 24 of whom had dark hair).
In a press statement, senior author Eva Schernhammer, PhD, of Harvard and the Medical University of Vienna, said the results “justify further prospective validation.”
She also explained that there are many variables to consider in this research, including different populations and countries, different susceptibility genotypes, different exposure settings (personal use vs. occupational exposure), and different colors of the permanent hair dyes used (dark dyes vs. light dyes).
Geographic location is a particularly important variable, suggested the study authors.
They pointed out that Europe, but not the United States, banned some individual hair dye ingredients that were considered carcinogenic during both the 1980s and 2000s. One country has even tighter oversight: “The most restrictive regulation of hair dyes exists in Japan, where cosmetic products are considered equivalent to drugs.”
The study was funded by the Centers for Disease Control and Prevention and the National Institute for Occupational Safety and Health. The study authors and Dr. White have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
The largest study of its kind has found no positive association between personal use of permanent hair dye and the risk for most cancers and cancer mortality.
The findings come from the Nurses’ Health Study, an ongoing prospective cohort study of more than 117,000 women who have been followed for 36 years and who did not have cancer at baseline.
The findings were published online on September 2 in the BMJ.
The results “offer some reassurance against concerns that personal use of permanent hair dyes might be associated with increased cancer risk or mortality,” write the investigators, with first author Yin Zhang, PhD, of Harvard Medical School, Boston.
The findings, which are limited to White women in the United States, indicate correlation, not causation, the authors emphasize.
Nevertheless, the researchers found an increased risk for some cancers among hair dye users, especially with greater cumulative dose (200 or more uses during the study period). The risk was increased for basal cell carcinoma, breast cancer (specifically, estrogen receptor negative [ER–], progesterone receptor negative [PR–], and hormone receptor negative [ER–, PR–]), and ovarian cancer.
A British expert not involved in the study dismissed these findings. “The reported associations are very weak, and, given the number of associations reported in this manuscript, they are very likely to be chance findings,” commented Paul Pharoah, PhD, professor of cancer epidemiology at the University of Cambridge (England).
“For the cancers where an increase in risk is reported, the results are not compelling. Even if they were real findings, the associations may not be cause-and-effect, and, even if they were causal associations, the magnitude of the effects are so small that any risk would be trivial.
“In short, none of the findings reported in this manuscript suggest that women who use hair dye are putting themselves at increased risk of cancer,” he stated.
A U.S. researcher who has previously coauthored a study suggesting an association between hair dye and breast cancer agreed that the increases in risk reported in this current study are “small.” But they are “of interest,” especially for breast and ovarian cancer, said Alexandra White, PhD, of the National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, N.C.
Hair dyes include compounds that “are not just potential carcinogens but also act as endocrine disruptors,” she said in an interview.
“In both breast and ovarian cancer, we know that hormones play an important part in the etiology ... so it’s biologically plausible that you would see [these associations in the current study],” added Dr. White, who was approached for comment.
However, she added that, even with the “modest” 20%-28% increase in the relative risk for certain breast cancers linked to a heavy cumulative dose of dyes in the current study, “there doesn’t seem to be any strong association with any cancer type.”
But she also pointed out that the most outstanding risk association was among ER–/PR– breast cancers, which are the “most aggressive and difficult to treat,” and thus the new findings are “important.”
Dr. White is the lead author of a 2019 study that received a lot of media attention because it rang an alarm bell about hair dyes and breast cancer risk.
That study concluded that ever using permanent hair dye or hair straighteners was associated with a higher risk for breast cancer than never using them and that this higher risk was especially associated with Black women. However, the study participants were from the prospective Sister Study. The participants in that study had no history of breast cancer, but they each had at least one sister who did. This family history of breast cancer may represent selection bias.
With changes in the 1980s, even safer now?
The study of hair dyes and cancer has “major public health implications” because the use of hair dye is widespread, Dr. Zhang and colleagues write in their article. They estimate that 50% to 80% of women and 10% of men aged 40 years and older in the United States and Europe use hair dye.
Permanent hair dyes “pose the greatest potential concern,” they stated, adding that these account for approximately 80% of hair dyes used in the United States and Europe and an even higher percentage in Asia.
The International Agency for Research on Cancer classifies occupational exposure to hair dyes as probably carcinogenic, but the carcinogenicity resulting from personal use of hair dyes is not classifiable – thus, there is no warning about at-home usage.
Notably, there was “a huge and very important” change in hair dye ingredients in the 1980s after the Food and Drug Administration warned about some chemicals in permanent hair dyes and the cosmetic industry altered their formulas, lead author Dr. Zhang said.
However, the researchers could not analyze use before and after the changes because not enough women reported first use of permanent hair dye after 1980 (only 1890 of 117,200 participants).
“We could expect that the current ingredients should make it safer,” Dr. Zhang said.
Study details
The researchers report that ever-users of permanent hair dyes had no significant increases in risk for solid cancers (n = 20,805; hazard ratio, 0.98, 95% confidence interval, 0.96-1.01) or hematopoietic cancers overall (n = 1,807; HR, 1.00; 95% CI, 0.91-1.10) compared with nonusers.
Additionally, ever-users did not have an increased risk for most specific cancers or cancer-related death (n = 4,860; HR, 0.96; 95% CI, 0.91-1.02).
As noted above, there were some exceptions.
Basal cell carcinoma risk was slightly increased for ever-users (n = 22,560; HR, 1.05; 95% CI, 1.02-1.08). Cumulative dose (a calculation of duration and frequency) was positively associated with risk for ER– breast cancer, PR– breast cancer, ER–/PR– breast cancer, and ovarian cancer, with risk rising in accordance with the total amount of dye.
Notably, at a cumulative dose of ≥200 uses, there was a 20% increase in the relative risk for ER- breast cancer (n = 1521; HR, 1.20; 95% CI, 1.02-1.41; P value for trend, .03). At the same cumulative dose, there was a 28% increase in the relative risk for ER-/PR- breast cancer (n = 1287; HR, 1.28, 95% CI, 1.08-1.52; P value for trend, .006).
In addition, an increased risk for Hodgkin lymphoma was observed, but only for women with naturally dark hair (the calculation was based on 70 women, 24 of whom had dark hair).
In a press statement, senior author Eva Schernhammer, PhD, of Harvard and the Medical University of Vienna, said the results “justify further prospective validation.”
She also explained that there are many variables to consider in this research, including different populations and countries, different susceptibility genotypes, different exposure settings (personal use vs. occupational exposure), and different colors of the permanent hair dyes used (dark dyes vs. light dyes).
Geographic location is a particularly important variable, suggested the study authors.
They pointed out that Europe, but not the United States, banned some individual hair dye ingredients that were considered carcinogenic during both the 1980s and 2000s. One country has even tighter oversight: “The most restrictive regulation of hair dyes exists in Japan, where cosmetic products are considered equivalent to drugs.”
The study was funded by the Centers for Disease Control and Prevention and the National Institute for Occupational Safety and Health. The study authors and Dr. White have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
Thromboembolic Events in Lung Cancer Patients Treated With Conventional Chemotherapy Alone Compared With Immunotherapy
PURPOSE: This retrospective analysis was designed to determine the incidence of venous and arterial thromboembolic events (TEEs) in lung cancer patients treated with either conventional chemotherapy (CC) alone, immunotherapy (IT) alone, or a combination of the two (C+I).
BACKGROUND: TEEs are a serious complication in cancer patients. Lung cancer is among the more thrombogenic malignancies and platinum-based chemotherapy used commonly in this setting is among the more thrombogenic CC regimens. IT and C+I have an increasing role among frontline management options for advanced stage lung cancers. However, the incidence of TEEs associated with IT agents has not been well characterized.
METHODS: Veterans with lung cancer were retrospectively identified in a VINCI CDW research database by ICD code. Treatment with CC and/or IT, and incidence of and time to TEEs (defined as deep vein thrombosis, pulmonary embolism, stroke, or myocardial infarction) were retrieved from the database using custom queries. Time to TEE was assessed relative to treatment start date, with censoring at a maximum of 180 days.
DATA ANALYSIS: We performed chi-squared tests and Kaplan-Meier time-to-event analyses among CC, C+I, and IT cohorts, controlling for platinum-containing v. non-platinum regimens. RESULTS: We identified 77,472 Veterans (97.7 % male, average age 66) with lung cancer treated between 1992-2019, 93.6% of whom received CC, while 4.5% and 1.9% received C+I or IT, respectively. We observed the highest rate of TEE in the IT cohort (13% v. 7.3% and 5.4% in the CC and C+I cohorts), and found that platinum-based chemotherapy decreased the likelihood of TEE (r = -3.13 and -4.06 for platinum-only and platinum-based with immunotherapy regimens), whereas IT strongly increased the likelihood of TEE (r = 8.05) (p<0.001). Finally, we confirm a decrease in time to TEE between the IT compared with CC and C+I cohorts (average 41 v. 57 and 65 days, respectively; <0.0001).
IMPLICATIONS: We found increased TEEs among lung cancer patients who received frontline IT compared with CC or C+I. With uncertainty in use of prophylactic anticoagulation for ambulatory cancer patients being treated with systemic therapy, cancer-associated TEE incidence and prevention in the IT setting warrants further evaluation.
PURPOSE: This retrospective analysis was designed to determine the incidence of venous and arterial thromboembolic events (TEEs) in lung cancer patients treated with either conventional chemotherapy (CC) alone, immunotherapy (IT) alone, or a combination of the two (C+I).
BACKGROUND: TEEs are a serious complication in cancer patients. Lung cancer is among the more thrombogenic malignancies and platinum-based chemotherapy used commonly in this setting is among the more thrombogenic CC regimens. IT and C+I have an increasing role among frontline management options for advanced stage lung cancers. However, the incidence of TEEs associated with IT agents has not been well characterized.
METHODS: Veterans with lung cancer were retrospectively identified in a VINCI CDW research database by ICD code. Treatment with CC and/or IT, and incidence of and time to TEEs (defined as deep vein thrombosis, pulmonary embolism, stroke, or myocardial infarction) were retrieved from the database using custom queries. Time to TEE was assessed relative to treatment start date, with censoring at a maximum of 180 days.
DATA ANALYSIS: We performed chi-squared tests and Kaplan-Meier time-to-event analyses among CC, C+I, and IT cohorts, controlling for platinum-containing v. non-platinum regimens. RESULTS: We identified 77,472 Veterans (97.7 % male, average age 66) with lung cancer treated between 1992-2019, 93.6% of whom received CC, while 4.5% and 1.9% received C+I or IT, respectively. We observed the highest rate of TEE in the IT cohort (13% v. 7.3% and 5.4% in the CC and C+I cohorts), and found that platinum-based chemotherapy decreased the likelihood of TEE (r = -3.13 and -4.06 for platinum-only and platinum-based with immunotherapy regimens), whereas IT strongly increased the likelihood of TEE (r = 8.05) (p<0.001). Finally, we confirm a decrease in time to TEE between the IT compared with CC and C+I cohorts (average 41 v. 57 and 65 days, respectively; <0.0001).
IMPLICATIONS: We found increased TEEs among lung cancer patients who received frontline IT compared with CC or C+I. With uncertainty in use of prophylactic anticoagulation for ambulatory cancer patients being treated with systemic therapy, cancer-associated TEE incidence and prevention in the IT setting warrants further evaluation.
PURPOSE: This retrospective analysis was designed to determine the incidence of venous and arterial thromboembolic events (TEEs) in lung cancer patients treated with either conventional chemotherapy (CC) alone, immunotherapy (IT) alone, or a combination of the two (C+I).
BACKGROUND: TEEs are a serious complication in cancer patients. Lung cancer is among the more thrombogenic malignancies and platinum-based chemotherapy used commonly in this setting is among the more thrombogenic CC regimens. IT and C+I have an increasing role among frontline management options for advanced stage lung cancers. However, the incidence of TEEs associated with IT agents has not been well characterized.
METHODS: Veterans with lung cancer were retrospectively identified in a VINCI CDW research database by ICD code. Treatment with CC and/or IT, and incidence of and time to TEEs (defined as deep vein thrombosis, pulmonary embolism, stroke, or myocardial infarction) were retrieved from the database using custom queries. Time to TEE was assessed relative to treatment start date, with censoring at a maximum of 180 days.
DATA ANALYSIS: We performed chi-squared tests and Kaplan-Meier time-to-event analyses among CC, C+I, and IT cohorts, controlling for platinum-containing v. non-platinum regimens. RESULTS: We identified 77,472 Veterans (97.7 % male, average age 66) with lung cancer treated between 1992-2019, 93.6% of whom received CC, while 4.5% and 1.9% received C+I or IT, respectively. We observed the highest rate of TEE in the IT cohort (13% v. 7.3% and 5.4% in the CC and C+I cohorts), and found that platinum-based chemotherapy decreased the likelihood of TEE (r = -3.13 and -4.06 for platinum-only and platinum-based with immunotherapy regimens), whereas IT strongly increased the likelihood of TEE (r = 8.05) (p<0.001). Finally, we confirm a decrease in time to TEE between the IT compared with CC and C+I cohorts (average 41 v. 57 and 65 days, respectively; <0.0001).
IMPLICATIONS: We found increased TEEs among lung cancer patients who received frontline IT compared with CC or C+I. With uncertainty in use of prophylactic anticoagulation for ambulatory cancer patients being treated with systemic therapy, cancer-associated TEE incidence and prevention in the IT setting warrants further evaluation.
A Case of Alectinib Cutaneous Toxicity and Results of a Desensitization Protocol
CASE REPORT: A male smoker aged 51 years with denovo metastatic NSCLC was treated with first-line chemoimmunotherapy. After 4 cycles, an EML4-ALK fusion was identified. At time of disease progression, alectinib 600mg BID was started after an 8-week washout period. Within 2 weeks, he developed a pruritic rash covering 90% of his BSA that required hospitalization and IV steroids. Biopsy confirmed a spongiotic and interface dermatitis with eosinophils consistent with a drug eruption. Rash was reported as an adverse event in the ALEX trial in 17% of patients treated with front-line alectinib but grade 3 rash was reported in only 1%.
A literature search demonstrated successful case reports of alectinib de-sensitization and thus a de-sensitization protocol was devised. Alectinib was started at 150mg daily and increased to 300mg BID over 2 weeks. His rash worsened resulting in a drug hold, treatment with oral prednisone, and a dose reduction to 300mg daily. The dose was increased to 300mg/450mg over 1 week when he developed painful mouth erosions. This resulted in a second dose hold and reduction to 300mg BID. After 2 weeks, alectinib was discontinued due to worsening rash with a plan to switch to an alternate ALK TKI, a strategy which has been successfully reported in the literature. Lorlatinib 100mg was recommended given phase 2 data demonstrating very low rates of rash (5% grade 1-2 and < 1% grade 3). While he did experience a facial rash within 2 weeks, a dose hold or reduction was not required. Nonetheless, lorlatinib was discontinued after 4 weeks due to other intolerable side effects and hypertriglyceridemia
DISCUSSION: Pembrolizumab has a terminal half-life of 22 days with steady state reached at 16 weeks with every 3-week dosing. It is therefore possible that prior exposure to pembrolizumab exacerbated the cutaneous toxicity of alectinib in this case. Multiple studies have shown that combining immunotherapy with alectinib leads to substantially more adverse events.
CONCLUSION: In patients with alectinib hypersensitivity, a de-sensitization protocol can be attempted. If hypersensitivity recurs, switching to an alternate ALK TKI is warranted. However, if immunotherapy has been previously administered without time for adequate washout, no TKI therapy may be tolerable.
CASE REPORT: A male smoker aged 51 years with denovo metastatic NSCLC was treated with first-line chemoimmunotherapy. After 4 cycles, an EML4-ALK fusion was identified. At time of disease progression, alectinib 600mg BID was started after an 8-week washout period. Within 2 weeks, he developed a pruritic rash covering 90% of his BSA that required hospitalization and IV steroids. Biopsy confirmed a spongiotic and interface dermatitis with eosinophils consistent with a drug eruption. Rash was reported as an adverse event in the ALEX trial in 17% of patients treated with front-line alectinib but grade 3 rash was reported in only 1%.
A literature search demonstrated successful case reports of alectinib de-sensitization and thus a de-sensitization protocol was devised. Alectinib was started at 150mg daily and increased to 300mg BID over 2 weeks. His rash worsened resulting in a drug hold, treatment with oral prednisone, and a dose reduction to 300mg daily. The dose was increased to 300mg/450mg over 1 week when he developed painful mouth erosions. This resulted in a second dose hold and reduction to 300mg BID. After 2 weeks, alectinib was discontinued due to worsening rash with a plan to switch to an alternate ALK TKI, a strategy which has been successfully reported in the literature. Lorlatinib 100mg was recommended given phase 2 data demonstrating very low rates of rash (5% grade 1-2 and < 1% grade 3). While he did experience a facial rash within 2 weeks, a dose hold or reduction was not required. Nonetheless, lorlatinib was discontinued after 4 weeks due to other intolerable side effects and hypertriglyceridemia
DISCUSSION: Pembrolizumab has a terminal half-life of 22 days with steady state reached at 16 weeks with every 3-week dosing. It is therefore possible that prior exposure to pembrolizumab exacerbated the cutaneous toxicity of alectinib in this case. Multiple studies have shown that combining immunotherapy with alectinib leads to substantially more adverse events.
CONCLUSION: In patients with alectinib hypersensitivity, a de-sensitization protocol can be attempted. If hypersensitivity recurs, switching to an alternate ALK TKI is warranted. However, if immunotherapy has been previously administered without time for adequate washout, no TKI therapy may be tolerable.
CASE REPORT: A male smoker aged 51 years with denovo metastatic NSCLC was treated with first-line chemoimmunotherapy. After 4 cycles, an EML4-ALK fusion was identified. At time of disease progression, alectinib 600mg BID was started after an 8-week washout period. Within 2 weeks, he developed a pruritic rash covering 90% of his BSA that required hospitalization and IV steroids. Biopsy confirmed a spongiotic and interface dermatitis with eosinophils consistent with a drug eruption. Rash was reported as an adverse event in the ALEX trial in 17% of patients treated with front-line alectinib but grade 3 rash was reported in only 1%.
A literature search demonstrated successful case reports of alectinib de-sensitization and thus a de-sensitization protocol was devised. Alectinib was started at 150mg daily and increased to 300mg BID over 2 weeks. His rash worsened resulting in a drug hold, treatment with oral prednisone, and a dose reduction to 300mg daily. The dose was increased to 300mg/450mg over 1 week when he developed painful mouth erosions. This resulted in a second dose hold and reduction to 300mg BID. After 2 weeks, alectinib was discontinued due to worsening rash with a plan to switch to an alternate ALK TKI, a strategy which has been successfully reported in the literature. Lorlatinib 100mg was recommended given phase 2 data demonstrating very low rates of rash (5% grade 1-2 and < 1% grade 3). While he did experience a facial rash within 2 weeks, a dose hold or reduction was not required. Nonetheless, lorlatinib was discontinued after 4 weeks due to other intolerable side effects and hypertriglyceridemia
DISCUSSION: Pembrolizumab has a terminal half-life of 22 days with steady state reached at 16 weeks with every 3-week dosing. It is therefore possible that prior exposure to pembrolizumab exacerbated the cutaneous toxicity of alectinib in this case. Multiple studies have shown that combining immunotherapy with alectinib leads to substantially more adverse events.
CONCLUSION: In patients with alectinib hypersensitivity, a de-sensitization protocol can be attempted. If hypersensitivity recurs, switching to an alternate ALK TKI is warranted. However, if immunotherapy has been previously administered without time for adequate washout, no TKI therapy may be tolerable.