Medicine Matters oncology

KEYNOTE-021 is a multicohort phase I/II study designed to examine the safety of pembrolizumab in combination with chemotherapy, immunotherapy or tyrosine kinase inhibitors. Cohort G was a randomized phase II expansion designed to explore the impact of adding pembrolizumab to pemetrexed and carboplatin in patients with stage IIIB or IV nonsquamous lung carcinoma without EGFR or ALK aberrations, but without PDL-1 selection [5]. This randomized phase II study of 123 patients met its primary endpoint of response rate, which favored the immunotherapy combination: 55% with the combination compared to 29% with chemotherapy alone (p=0.0016). Secondary endpoints included improved progression-free survival with a hazard ratio of 0.53 (95% CI 0.31-0.91). Toxicity, however, was additive, with 39% of patients in the combination arm experiencing ≥ grade 3 toxicity compared to 26% of those receiving chemotherapy alone. Despite this, toxicity appeared manageable, as the rate of discontinuation due to drug-related toxicity was similar in both arms: 13% with chemotherapy and 10% with chemotherapy plus pembrolizumab. Quality of life was not measured. There was no difference in overall survival (OS HR 0.90, p=0.39) with a median follow-up of 10.6 months. Updates to this dataset have been presented and the survival HR has numerically improved, with a median follow-up of 14.5 months (OS HR 0.69, p=0.13) [6] and 18.7 months (OS HR 0.59, p=0.03), although the confidence intervals overlap and the difference is not statistically significant [7].