Phase 1/2 Trial of Pembrolizumab and Concurrent Chemoradiation Therapy for Limited-Stage SCLC
| Autor: | Bonnie S. Glisson, Joe Y. Chang, Vassiliki A. Papadimitrakopoulou, John V. Heymach, Katherine Klein, George R. Simon, Vivek Verma, James W. Welsh, Roshal R. Patel, Jianjun Zhang, Ferdinandos Skoulidis, Chunxiao Guo, Taylor R. Cushman, Quynh Nhu Nguyen, Mehmet Altan, Tugce Ozgen, Hari Menon, Girish S. Shroff, Lauren Averett Byers, Dawei Chen, Nathan Comeaux, Chad Tang, Melenda Jeter, Kenneth R. Hess |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Pulmonary and Respiratory Medicine Oncology Adult medicine.medical_specialty Lung Neoplasms medicine.medical_treatment Pembrolizumab Neutropenia Antibodies Monoclonal Humanized 03 medical and health sciences 0302 clinical medicine Internal medicine Antineoplastic Combined Chemotherapy Protocols medicine Clinical endpoint Humans Performance status business.industry Common Terminology Criteria for Adverse Events Chemoradiotherapy medicine.disease Small Cell Lung Carcinoma Confidence interval Radiation therapy 030104 developmental biology 030220 oncology & carcinogenesis Prophylactic cranial irradiation Cisplatin business |
| Zdroj: | Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer. 15(12) |
| ISSN: | 1556-1380 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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