Treatment Design and Rationale for a Randomized Trial of Cisplatin and Etoposide Plus Thoracic Radiotherapy Followed by Nivolumab or Placebo for Locally Advanced Non-Small-Cell Lung Cancer (RTOG 3505)

• Authors: David E. Gerber, University of Texas; James J. Urbanic, University of California San Diego; Corey Langer, University of Pennsylvania; Chen Hu, Johns Hopkins University; I-Fen Chang, Bristol-Myers Squibb; Bo Lu, Thomas Jefferson University; Benjamin Movsas, Henry Ford Hospital; Robert Jeraj, University of Wisconsin; Walter J Curran, Emory University; Jeffrey D. Bradley, Washington University
• Journal Title: Clinical Lung Cancer
• Volume: Volume 18, Number 3
• Publisher: Elsevier: 12 months | 2017-05-01, Pages 333-339
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1016/j.cllc.2016.10.009
• Subjects: Health Sciences, Oncology; Health Sciences, Pharmacy
• Keywords: Science & Technology; Life Sciences & Biomedicine; Oncology; Abscopal effect; Checkpoint inhibitor; Coprimary end points; Immunotherapy; Programmed death 1 (PD-1); PHASE-III TRIAL; CONCURRENT; DOCETAXEL; TUMORS; CHEMORADIOTHERAPY; CONSOLIDATION; CARBOPLATIN; RADIATION; PACLITAXEL; THERAPY

Abstract

Radiation Therapy Oncology Group (RTOG) 3505 is a randomized phase 3 study of concurrent chemoradiation followed by immune checkpoint inhibitor therapy or placebo in patients with locally advanced non–small-cell lung cancer (NSCLC). Patients with surgically unresectable stage 3 NSCLC will receive thoracic radiotherapy to 60 Gy with concurrent cisplatin 50 mg/m 2 intravenously (I.V.) on days 1, 8, 29, and 36, and etoposide 50 mg/m 2 I.V. on days 1 to 5 and days 29 to 33. Between 4 and 12 weeks after completion of concurrent chemoradiation, eligible patients will be randomized to the anti–programmed death 1 (PD-1) monoclonal antibody nivolumab 240 mg I.V. or placebo every 2 weeks for up to 1 year. The primary end points are overall survival (OS) and progression-free survival (PFS), as determined by central independent radiology review. Secondary objectives include toxicity assessment, patient-reported outcomes and quality of life, and OS and PFS in programmed death ligand 1 (PD-L1) expressors (≥ 1%) and PD-L1 nonexpressors ( < 1%). Assuming a rate of 16.7% due to ineligibility and dropout before randomization, a total of 660 patients will be enrolled to ensure 550 patients will be randomized after completion of chemoradiation. This sample size will provide ≥ 90% power to detect a hazard ratio of 0.7 for OS with 2-sided type I error of 0.04, and to detect a hazard ratio of 0.667 for PFS 2-sided type I error of 0.01. (NCT02768558)