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Combination pembrolizumab and chemoradiotherapy appears safe and active for patients with locally advanced non–small cell lung cancer (NSCLC), results from a phase 1 trial suggest.
Nearly 90% of evaluable patients responded to the combination, and the 12-month progression-free survival rate was 69.7%. Pneumonitis was common, but most patients responded to high-dose corticosteroids.
Salma K. Jabbour, MD, of Rutgers Cancer Institute of New Jersey, in New Brunswick, and colleagues reported these results in JAMA Oncology.
The phase 1 study included 21 patients with locally advanced, unresectable, stage III NSCLC. Planned treatment consisted of pembrolizumab (Keytruda) at various dosing schedules, chemotherapy (weekly carboplatin and paclitaxel), and radiation (2 Gy/day, 60 Gy total).
The researchers used a standard 3 + 3 design to evaluate the safety and tolerability of pembrolizumab in five dosing cohorts.
In cohort 1, patients received pembrolizumab at 200 mg every 21 days within 2-6 weeks of completing chemoradiotherapy. In cohort 2, patients received pembrolizumab at 100 mg every 21 days, starting on day 29 of chemoradiotherapy. Cohort 3 received the 200 mg dose of pembrolizumab, starting on day 29.
Pembrolizumab was started on day 1 of chemoradiotherapy at the 100-mg dose in cohort 4 and at the 200-mg dose in cohort 5. An additional six-patient safety expansion cohort received the same treatment as cohort 5.
The median follow-up was 16 months. There was one dose-limiting toxicity – grade 5 pneumonitis, which occurred in the safety expansion cohort.
Grade 2 or higher immune-related toxicities were observed in 14 patients (67%), and grade 2 or higher pneumonitis occurred in 7 patients (33%).
“Although we observed an increased rate of pneumonitis, most patients had pneumonitis that responded to high-dose corticosteroid treatment,” the researchers noted.
There were 19 patients who received at least two cycles of pembrolizumab and were evaluable for response. The best response was complete response in 3 patients (16%), partial response in 14 patients (74%), and stable disease in 1 patient (5%).
The progression-free survival rate was 81.0% at 6 months and 69.7% at 12 months. The overall survival rate was 95.2% at 6 months and 85.2% at 12 months.
The researchers acknowledged that two key limitations of this study were the small sample size and short duration of follow-up.
“Pembrolizumab with concurrent chemoradiotherapy is tolerable for patients with locally advanced, unresectable NSCLC, although the risk of pneumonitis and long-term outcomes should be evaluated in additional studies,” commented Enriqueta Felip, MD, PhD, of Vall D’Hebron Institute of Oncology in Barcelona, who was not involved in this study.
The study was funded by Merck. The authors and Dr. Felip disclosed relationships with Merck and other companies.
SOURCE: Jabbour SK et al. JAMA Oncol. 2020 Feb 20. doi: 10.1001/jamaoncol.2019.6731.
Combination pembrolizumab and chemoradiotherapy appears safe and active for patients with locally advanced non–small cell lung cancer (NSCLC), results from a phase 1 trial suggest.
Nearly 90% of evaluable patients responded to the combination, and the 12-month progression-free survival rate was 69.7%. Pneumonitis was common, but most patients responded to high-dose corticosteroids.
Salma K. Jabbour, MD, of Rutgers Cancer Institute of New Jersey, in New Brunswick, and colleagues reported these results in JAMA Oncology.
The phase 1 study included 21 patients with locally advanced, unresectable, stage III NSCLC. Planned treatment consisted of pembrolizumab (Keytruda) at various dosing schedules, chemotherapy (weekly carboplatin and paclitaxel), and radiation (2 Gy/day, 60 Gy total).
The researchers used a standard 3 + 3 design to evaluate the safety and tolerability of pembrolizumab in five dosing cohorts.
In cohort 1, patients received pembrolizumab at 200 mg every 21 days within 2-6 weeks of completing chemoradiotherapy. In cohort 2, patients received pembrolizumab at 100 mg every 21 days, starting on day 29 of chemoradiotherapy. Cohort 3 received the 200 mg dose of pembrolizumab, starting on day 29.
Pembrolizumab was started on day 1 of chemoradiotherapy at the 100-mg dose in cohort 4 and at the 200-mg dose in cohort 5. An additional six-patient safety expansion cohort received the same treatment as cohort 5.
The median follow-up was 16 months. There was one dose-limiting toxicity – grade 5 pneumonitis, which occurred in the safety expansion cohort.
Grade 2 or higher immune-related toxicities were observed in 14 patients (67%), and grade 2 or higher pneumonitis occurred in 7 patients (33%).
“Although we observed an increased rate of pneumonitis, most patients had pneumonitis that responded to high-dose corticosteroid treatment,” the researchers noted.
There were 19 patients who received at least two cycles of pembrolizumab and were evaluable for response. The best response was complete response in 3 patients (16%), partial response in 14 patients (74%), and stable disease in 1 patient (5%).
The progression-free survival rate was 81.0% at 6 months and 69.7% at 12 months. The overall survival rate was 95.2% at 6 months and 85.2% at 12 months.
The researchers acknowledged that two key limitations of this study were the small sample size and short duration of follow-up.
“Pembrolizumab with concurrent chemoradiotherapy is tolerable for patients with locally advanced, unresectable NSCLC, although the risk of pneumonitis and long-term outcomes should be evaluated in additional studies,” commented Enriqueta Felip, MD, PhD, of Vall D’Hebron Institute of Oncology in Barcelona, who was not involved in this study.
The study was funded by Merck. The authors and Dr. Felip disclosed relationships with Merck and other companies.
SOURCE: Jabbour SK et al. JAMA Oncol. 2020 Feb 20. doi: 10.1001/jamaoncol.2019.6731.
Combination pembrolizumab and chemoradiotherapy appears safe and active for patients with locally advanced non–small cell lung cancer (NSCLC), results from a phase 1 trial suggest.
Nearly 90% of evaluable patients responded to the combination, and the 12-month progression-free survival rate was 69.7%. Pneumonitis was common, but most patients responded to high-dose corticosteroids.
Salma K. Jabbour, MD, of Rutgers Cancer Institute of New Jersey, in New Brunswick, and colleagues reported these results in JAMA Oncology.
The phase 1 study included 21 patients with locally advanced, unresectable, stage III NSCLC. Planned treatment consisted of pembrolizumab (Keytruda) at various dosing schedules, chemotherapy (weekly carboplatin and paclitaxel), and radiation (2 Gy/day, 60 Gy total).
The researchers used a standard 3 + 3 design to evaluate the safety and tolerability of pembrolizumab in five dosing cohorts.
In cohort 1, patients received pembrolizumab at 200 mg every 21 days within 2-6 weeks of completing chemoradiotherapy. In cohort 2, patients received pembrolizumab at 100 mg every 21 days, starting on day 29 of chemoradiotherapy. Cohort 3 received the 200 mg dose of pembrolizumab, starting on day 29.
Pembrolizumab was started on day 1 of chemoradiotherapy at the 100-mg dose in cohort 4 and at the 200-mg dose in cohort 5. An additional six-patient safety expansion cohort received the same treatment as cohort 5.
The median follow-up was 16 months. There was one dose-limiting toxicity – grade 5 pneumonitis, which occurred in the safety expansion cohort.
Grade 2 or higher immune-related toxicities were observed in 14 patients (67%), and grade 2 or higher pneumonitis occurred in 7 patients (33%).
“Although we observed an increased rate of pneumonitis, most patients had pneumonitis that responded to high-dose corticosteroid treatment,” the researchers noted.
There were 19 patients who received at least two cycles of pembrolizumab and were evaluable for response. The best response was complete response in 3 patients (16%), partial response in 14 patients (74%), and stable disease in 1 patient (5%).
The progression-free survival rate was 81.0% at 6 months and 69.7% at 12 months. The overall survival rate was 95.2% at 6 months and 85.2% at 12 months.
The researchers acknowledged that two key limitations of this study were the small sample size and short duration of follow-up.
“Pembrolizumab with concurrent chemoradiotherapy is tolerable for patients with locally advanced, unresectable NSCLC, although the risk of pneumonitis and long-term outcomes should be evaluated in additional studies,” commented Enriqueta Felip, MD, PhD, of Vall D’Hebron Institute of Oncology in Barcelona, who was not involved in this study.
The study was funded by Merck. The authors and Dr. Felip disclosed relationships with Merck and other companies.
SOURCE: Jabbour SK et al. JAMA Oncol. 2020 Feb 20. doi: 10.1001/jamaoncol.2019.6731.
FROM JAMA ONCOLOGY