Phase I/II Trial of Pembrolizumab and Concurrent Chemoradiation Therapy for Limited-Stage Small Cell Lung Cancer.

Welsh, James W; Heymach, John V; Guo, Chunxiao; Menon, Hari; Klein, Katherine; Cushman, Taylor R; Verma, Vivek; Hess, Kenneth R; Shroff, Girish; Tang, Chad; Skoulidis, Ferdinandos; Jeter, Melenda; Comeaux, Nathan; Patel, Roshal R; Chen, Dawei; Ozgen, Tugce; Nguyen, Quynh-Nhu; Chang, Joe Y; Altan, Mehmet; Zhang, Jianjun; Papadimitrakopoulou, Vassiliki A; Simon, George R; Byers, Lauren A; Glisson, Bonnie

PURPOSE Few advancements in treating limited-stage small cell lung cancer (LS-SCLC) have been made in decades. We report here a phase I/II trial of concurrent chemoradiotherapy (CRT) and pembrolizumab. METHODS This single-center, open-label phase I/II study recruited adults with LS-SCLC or other neuroendocrine tumors and good performance status (ECOG ≤2). The primary endpoint was safety, as assessed by dose-limiting toxicities (DLTs). Concurrent CRT consisted of etoposide and a platin with 45 Gy radiotherapy (30 BID). Prophylactic cranial irradiation (25 Gy, 10 fractions) was given at the physician's discretion. Pembrolizumab was started concurrently with CRT and continued for up to 16 cycles. The phase I portion consisted of a 3+3 design. Toxicity was assessed with CTCAE v4.0. Secondary outcomes were progression-free survival (PFS), overall survival (OS), and tumor response as measured by the IRRC. RESULTS Forty-five patients were screened and 40 were enrolled. All completed RT and received ≥1 cycle of pembrolizumab. Twenty-seven (61%) received PCI. One DLT was observed in the phase I portion. There were no grade 5 toxicities, and three grade 4 events (2 neutropenia, 1 respiratory failure). The pneumonitis rate was 15% (three grade 2 and three grade 3). All 17 (42.5%) esophagitis events were grades 1-2. At median follow-up time of 23.1 months, the median PFS time was 19.7 months (95% confidence interval [CI] 8.8‒30.5) and median OS time was 39.5 months (95% CI 8.0‒71.0). CONCLUSION Concurrent CRT and pembrolizumab for LS-SCLC was well tolerated and yielded favorable outcomes, providing a basis for randomized studies.