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] 8.8â30.5) and median OS time was 39.5 months (95% CI 8.0â71.0).
CONCLUSION: Concurrent CRT and pembrolizumab for LS-SCLC was well tolerated and yielded favorable outcomes, providing a basis for randomized studies.