Standard Thoracic Radiotherapy with or without Concurrent Daily Low-Dose Carboplatin in Elderly Patients with Locally Advanced Non-Small Cell Lung Cancer: A Phase III Trial of the Japan Clinical Oncology Group (JCOG0301)

Background The standard treatment of locally advanced non-small cell lung cancer (NSCLC) has been considered to be chemo-radiotherapy (CRT). However, the benefit of this combined therapy for elderly patients (patients) is still unclear. This trial was set up to evaluate whether thoracic radiotherapy (RT) with daily low-dose carboplatin (CBDCA) would result in longer survival in elderly patients with unresectable stage III NSCLC than RT alone (JCOG0301). Methods Patients older than 70 years with unresectable stage III NSCLC were randomized to either RT alone (RT arm), a total dose of 60 Gy, or CRT arm including the same RT plus concurrent chemotherapy with carboplatin 30 mg/m2/day, 5 days/week for 20 days. The primary end point was overall survival (OS). The planned sample size was 100 patients in each arm with one-sided alpha of 5% and 80% power to detect a difference in median survival time (MST) from 10 months in the RT arm to 15 months in the CRT arm. Results Between September 2003 and May 2010, 200 patients were randomized. Baseline characteristics were similar in the RT (n = 100) versus CRT (n = 100) arms: median age, 77 versus 77 years; stage IIIB (n), 46 versus 49; PS 0/1/2 (n), 41/55/4 versus 41/56/3. The second planned interim analysis was carried out 10 months after the completion of accrual. In accordance with the pre-specified stopping rule, the JCOG Data and Safety Monitoring Committee recommended early publication of this trial because of the difference in OS favoring the CRT arm. In the updated analysis, OS was better in the CRT arm than the RT arm (HR = 0.64, 95% CI = 0.46–0.89, one-sided P = 0.0033 by stratified log-rank test). In each arm (RT/CRT), MST was 16.5 months/22.4 months with 3-year OS of 14.3%/34.6%, response rate of 44.9%/54.6% (P = 0.201) and median progression-free survival of 6.9 months/8.9 months (P = 0.003). Grade 3/4 toxic effects were (RT/CRT): neutropenia 0%/57.3%, infection 4.1%/12.5%, dysphagia 0%/1.0%, late RT toxic effects 7.4%/7.5%. The pattern of relapse site and post-protocol treatment were almost similar between the arms. Even after an adjustment by the Cox regression analysis with six variables (stage, PS, sex, age, histology, smoking status), the CRT arm showed better survival (HR = 0.71, P = 0.038).