A randomised phase 2b study comparing the efficacy and safety of belotecan vs. topotecan as monotherapy for sensitive-relapsed small-cell lung cancer.

ABSTRACT

BACKGROUND: This study compared the efficacy/safety of the camptothecin analogues belotecan and topotecan for sensitive-relapsed small-cell lung cancer (SCLC). METHODS: One-hundred-and-sixty-four patients were randomised (11) to receive five consecutive daily intravenous infusions of topotecan (1.5 mg/m2) or belotecan (0.5 mg/m2), every 3 weeks, for six cycles. Main outcomes were objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), tolerability and toxicity. The study statistical plan was non-inferiority design with ORR as the endpoint. RESULTS: In the belotecan vs. topotecan groups, ORR (primary endpoint) was 33% vs. 21% (p = 0.09) and DCR was 85% vs. 70% (p = 0.030). PFS was not different between groups. Median OS was significantly longer with belotecan than with topotecan (13.2 vs. 8.2 months, HR = 0.69, 95% CI 0.48-0.99), particularly in patients aged <65 years, with more advanced disease (i.e., extensive-stage disease, time to relapse 3-6 months), or Eastern Cooperative Oncology Group performance status 1 or 2. More belotecan recipients completed all treatment cycles (53% vs. 35%; p = 0.022). CONCLUSIONS: The efficacy/safety of belotecan warrants further evaluation in Phase 3 trials. Belotecan potentially offers an alternative to topotecan for sensitive-relapsed SCLC, particularly in patients aged <65 years, with more advanced disease, or poor performance.