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

• Published in: Cancer Vol. 129; no. 2; pp. 264 - 271
• Main Authors: Salous, Tareq, Shukla, Nikhil A., Althouse, Sandra K., Perkins, Susan M., Furqan, Muhammad, Leal, Ticiana, Traynor, Anne M., Feldman, Lawrence E., Hanna, Nasser H., Durm, Greg A.
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 15.01.2023
• Subjects: Adenocarcinoma; Anemia; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Cancer research; Carcinoma, Non-Small-Cell Lung - pathology; Chemotherapy; docetaxel; Female; Health services; Humans; Hypotheses; Immune checkpoint inhibitors; Immune Checkpoint Inhibitors - therapeutic use; Immunotherapy; Inhibitors; Lung cancer; Lung Neoplasms - pathology; Male; Monoclonal antibodies; Mutation; Non-small cell lung carcinoma; non–small cell lung cancer; Null hypothesis; Oncology; Patients; PD-L1 protein; Pembrolizumab; pemetrexed; Programmed Cell Death 1 Receptor - therapeutic use; second‐line chemotherapy; Small cell lung carcinoma; Smoking; Solid tumors; Squamous cell carcinoma; Statistical analysis; Survival; Targeted cancer therapy; Toxicity; Tumors; non-small cell lung cancer; pembrolizumab; pemetrexed; docetaxel; second-line chemotherapy
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.34565

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 < .05). The median PFS was 5.1 months (95% confidence interval [CI], 3.6–8.0 months). The median OS was 24.5 months (95% CI, 15.6–30.9 months). The most common treatment‐related adverse events were fatigue (60%), anemia (54.3%), and nausea (42.9%). There were no treatment‐related deaths. Conclusions Pembrolizumab plus next‐line chemotherapy in patients with advanced NSCLC who experienced PD after a clinical benefit from a CPI was associated with statistically significant higher PFS in comparison with historical controls of single‐agent chemotherapy alone. Pembrolizumab plus next‐line chemotherapy in patients with advanced non–small cell lung cancer who experienced progressive disease after a clinical benefit from a checkpoint inhibitor was associated with statistically significant higher progression‐free survival in comparison with a historical control of single‐agent chemotherapy.