A phase 2 trial of chemotherapy plus pembrolizumab in patients with advanced non–small cell lung cancer previously treated with a PD‐1 or PD‐L1 inhibitor: Big Ten Cancer Research Consortium BTCRC‐LUN15‐029

Background Immunotherapy using a checkpoint inhibitor (CPI) alone or in combination with chemotherapy is the standard of care for treatment‐naive patients with advanced non–small cell lung cancer (NSCLC) without driver mutations for which targeted therapies have been approved. It is unknown whether continuing CPI treatment beyond disease progression results in improved outcomes. Methods Patients who experienced progressive disease (PD) after a clinical benefit from chemotherapy plus a CPI were enrolled. Patients received pembrolizumab (200 mg every 3 weeks) plus next‐line chemotherapy. The primary end point was progression‐free survival (PFS) according to the Response Evaluation Criteria in Solid Tumors (version 1.1). Key secondary end points included the overall survival (OS), clinical benefit rate, and toxicity. The authors’ hypothesis was that continuing pembrolizumab beyond progression would improve the median PFS to 6 months in comparison with a historical control of 3 months with single‐agent chemotherapy alone. Results Between May 2017 and February 2020, 35 patients were enrolled. The patient and disease characteristics were as follows: 51.4% were male; 82.9% were current or former smokers; and 74.3%, 20%, and 5.7% had adenocarcinoma, squamous cell carcinoma, and NSCLC not otherwise specified, respectively. The null hypothesis that the median PFS would be 3 months was rejected (p