This study compared the efficacy/safety of the camptothecin analogues belotecan and topotecan for sensitive-relapsed small-cell lung cancer (SCLC).
One-hundred-and-sixty-four patients were randomised (1:1) 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.
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).
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.
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We thank the participating patients and their families, the study investigators and the research coordinators. We also thank David P. Figgitt, PhD, ISMPP CMPP™, Content Ed Net Quest, for providing writing assistance and language support, with funding from Chong Kun Dang Pharmaceutical Corp., Seoul, South Korea.
Ethics approval and consent to participate
The study was conducted in accordance with the principles of the Declaration of Helsinki. It was registered with ClinicalTrials.gov (NCT01497873) and approved by the Institutional Review Board (IRB) of each participating institution (individual IRB committees are listed in the Supplementary File). All participants gave their informed consent prior to study inclusion.
The data are available for all study authors. The datasets used and analysed during the current study are available from the corresponding author on reasonable request.
The authors declare no competing financial interests.
This work was sponsored by Chong Kun Dang Pharmaceutical Corp., Seoul, South Korea.
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Kang, JH., Lee, KH., Kim, DW. et al. A randomised phase 2b study comparing the efficacy and safety of belotecan vs. topotecan as monotherapy for sensitive-relapsed small-cell lung cancer. Br J Cancer 124, 713–720 (2021). https://doi.org/10.1038/s41416-020-01055-5