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

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

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1919-1927
Number of pages9
JournalJournal of Thoracic Oncology
Volume15
Issue number12
DOIs
StatePublished - Dec 2020

Keywords

  • Immunotherapy
  • PD-1
  • PD-L1
  • Radiation therapy
  • SCLC

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

MD Anderson CCSG core facilities

  • Biostatistics Resource Group
  • Clinical Trials Office

Fingerprint

Dive into the research topics of 'Phase 1/2 Trial of Pembrolizumab and Concurrent Chemoradiation Therapy for Limited-Stage SCLC'. Together they form a unique fingerprint.

Cite this