Phase 1/2 Trial of Pembrolizumab and Concurrent Chemoradiation Therapy for Limited-Stage SCLC.

Autor:	Welsh JW; Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. Electronic address: jwelsh@mdanderson.org., Heymach JV; Department of Thoracic Head & Neck Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Guo C; Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Menon H; Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Klein K; Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Cushman TR; Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Verma V; Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Hess KR; Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas., Shroff G; Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Tang C; Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Skoulidis F; Department of Thoracic Head & Neck Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Jeter M; Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Comeaux N; Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Patel RR; Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Chen D; Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Ozgen T; Department of Radiation Oncology, Ankara University School of Medicine, Ankara, Turkey., Nguyen QN; Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Chang JY; Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Altan M; Department of Thoracic Head & Neck Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Zhang J; Department of Thoracic Head & Neck Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Papadimitrakopoulou VA; Department of Thoracic Head & Neck Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Simon GR; Department of Thoracic Head & Neck Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Byers LA; Department of Thoracic Head & Neck Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Glisson B; Department of Thoracic Head & Neck Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Jazyk:	angličtina
Zdroj:	Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer [J Thorac Oncol] 2020 Dec; Vol. 15 (12), pp. 1919-1927. Date of Electronic Publication: 2020 Sep 08.
DOI:	10.1016/j.jtho.2020.08.022
Abstrakt:	Introduction: Few advancements in treating limited-stage SCLC (LS-SCLC) have been made in decades. We report here a phase 1/2 trial of concurrent chemoradiotherapy (CRT) and pembrolizumab. Methods: This single-center, open-label phase 1/2 study recruited adults with LS-SCLC or other neuroendocrine tumors and good performance status (Eastern Cooperative Oncology Group ≤ 2). The primary end point was safety, as assessed by dose-limiting toxicities. Concurrent CRT consisted of etoposide and a platin with 45 Gy radiotherapy (30 twice daily). 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 1 portion consisted of a 3 + 3 design. Toxicity was assessed with Common Terminology Criteria for Adverse Events version 4.0. Secondary outcomes were progression-free survival, overall survival, and tumor response as measured by the immune-related response criteria. Results: A total of 45 patients were screened, and 40 were enrolled. All completed radiation therapy and received greater than or equal to one cycle of pembrolizumab. A total of 27 (61%) received percutaneous coronary intervention. One dose-limiting toxicity was observed in the phase 1 portion. There were no grade 5 toxicities, but there were three grade 4 events (two neutropenia, one respiratory failure). Pneumonitis rate was 15% (three grade 2 and three grade 3). All 17 esophagitis events (42.5%) were grades 1 to 2. At median follow-up time of 23.1 months, the median progression-free survival time was 19.7 months (95% confidence interval: 8.8‒30.5) and the median overall survival time was 39.5 months (95% confidence interval: 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. (Copyright © 2020 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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