A randomized phase II/III study comparing carboplatin and irinotecan with carboplatin and etoposide for the treatment of elderly patients with extensive-disease small cell lung cancer (JCOG1201/TORG1528).

8571 Background: Carboplatin and etoposide is the current standard treatment for elderly extensive-disease small-cell lung cancer (ED-SCLC). The purpose of this study is to evaluate the efficacy and safety of carboplatin and irinotecan compared with carboplatin and etoposide in elderly Japanese patients with ED-SCLC in a randomized phase II/III design. Methods: Eligibility included histologically or cytologically proven SCLC, no previous systemic chemotherapy, performance status of 0 to 2, and aged 71 years or older. Patients received carboplatin (AUC 5 mg/ml/min on day 1) and etoposide (80 mg/m 2 on day 1 to 3) (CE) every 3 weeks for 4 cycles or carboplatin (AUC 4 mg/ml/min on day 1) and irinotecan (50 mg/m 2 on day 1 and 8) (CI) every 3 weeks for 4 cycles. In the phase II part, the primary endpoint was the objective response rate of the CI arm and the secondary endpoint was adverse events. In the phase III part, the primary endpoint was overall survival, and the secondary endpoints were progression-free survival, objective response rate, adverse events, and symptom score. This study was designed to confirm the superiority of CI arm in terms of overall survival over CE arm. The median survival time with CI arm was expected to be increased by 3.5 months with hazard ratio (HR) of 0.750 (10.5 vs. 14.0 months). The sample size was set at 250 to observe the required number of events of 227 with one-sided alpha level of 0.05, a power of 70%, an accrual period of 6.5 years, and a follow-up period of 1.5 years. Results: Between December 2013 and June 2019, 258 patients were randomized (CE arm, 129 patients; CI arm, 129 patients). The median age was 75 (range, 71-90). The characteristics of the patients were well balanced between CE arm and CI arm. Overall survival, progression-free survival, and objective response rate of CE arm vs. CI arm were 12.0 (95% CI, 9.3-13.7) vs. 13.2 (95% CI, 11.1-14.6) months (HR, 0.848 (95% CI, 0.650-1.105)) (one-sided P=0.11), 4.4 (95% CI, 4.0-4.7) vs. 4.9 months (95% CI, 4.5-5.2) (HR, 0.851 (95% CI, 0.664-1.090)) (two-sided P=0.21), and 59.7% (77 of 129) vs. 64.3% (83 of 129), respectively. Symptom score showed no significant difference between the arms. Higher incidences of myelosuppression of grade 3 or worse occurred with CE arm, whereas higher incidences of gastrointestinal toxicity of grade 3 or worse occurred with CI arm. Three treatment-related deaths including lung infection in CE arm and lung infection and sepsis in CI arm were observed. Conclusions: Efficacy tended to be favorable in carboplatin and irinotecan arm, but there was no statistically significant difference. These results indicate that carboplatin and etoposide is a still standard treatment in elderly Japanese patients with ED-SCLC. Clinical trial information: 000012605.