Results from the phase 2 Keynote-799 trial show that addition of pembrolizumab to concurrent chemoradiation in patients with unresectable, stage IIIA-C NSCLC leads to objective response rates (ORR) that exceeded 50%, researchers reported at the virtual meeting of the American Society of Clinical Oncology.

Concurrent platinum doublet chemotherapy with radiotherapy is the first-line standard of care for patients with unresectable, stage III NSCLC. However, this approach provides a low five-year overall survival rate. The Keynote-799 trial, therefore, evaluated the addition of pembrolizumab to this first-line therapy. Patients in cohort A (n=112) received 1 cycle of pembrolizumab plus chemotherapy (paclitaxel/carboplatin), 2 cycles of immunochemotherapy plus concurrent radiotherapy, followed by up to 14 cycles pembrolizumab. Patients in cohort B (n=73, still recruiting) received 1 cycle of pembrolizumab plus chemotherapy (pemetrexed/cisplatin), 2 cycles of immunochemotherapy plus concurrent radiotherapy followed by up to 14 cycles pembrolizumab.

“Objective response rate, the primary endpoint of the trial, was 67.0% in cohort A and 56.6% in cohort B, predominantly partial responses”, reported Salma Jabbour, Professor of Radiation Oncology at Rutgers Cancer Institute, New Brunswick, USA. Median duration of response has not yet been reached in both cohorts. Progression-free survival rate at 6 months was 81.4% in Cohort A and 85.2% in Cohort B. Overall survival rates at 6 months were 87.2% and 94.8% in Cohort A and Cohort B, respectively.

“The study’s second primary objective was the incidence of grade 3 or higher pneumonitis. In both cohorts the rate of grade 3 or higher pneumonitis was less than 10%. One patient in Cohort B had interstitial lung disease. Four patients in Cohort A and none in Cohort B had treatment related grade 5 pneumonitis”, reported Prof. Jabbour. The incidence of other adverse events was consistent with the toxicity profiles of pembrolizumab monotherapy and advanced NSCLC and concurrent chemoradiotherapy in stage III NSCLC.

“Pembrolizumab plus concurrent chemoradiation shows promising anti-tumor activity in patients with unresectable locally advanced stage III NSCLC with an acceptable toxicity profile”, concluded Prof. Jabbour.

 

Jabbour SK et al. ASCO 2020 virtual meeting, abstract 9008.