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).
Gerber DE, Urbanic JJ, Langer C, Hu C, Chang IF, Lu B, Movsas B, Jeraj R, Curran WJ, and Bradley JD. 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). Clin Lung Cancer 2017 May;18(3):333-339.
Clinical lung cancer
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/m2 intravenously (I.V.) on days 1, 8, 29, and 36, and etoposide 50 mg/m2 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).
Medical Subject Headings
Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Chemoradiotherapy; Cisplatin; Combined Modality Therapy; Etoposide; Humans; Immunotherapy; Lung Neoplasms; Middle Aged; Neoplasm Staging; Nivolumab; Placebo Effect; Proportional Hazards Models; Research Design; Survival Analysis; Young Adult