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Clinical Study

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 (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.

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.

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Fig. 1: Waterfall plots demonstrating the efficacy of belotecan and topotecan monotherapy in patients with sensitive-relapsed SCLC.
Fig. 2: Survival curves for belotecan and topotecan.
Fig. 3: Forest plot showing HR of belotecan relative to topotecan for OS in different subgroups.

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Acknowledgements

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.

Author information

Affiliations

Authors

Contributions

J.-H.Kang: drafted and revised the paper for important intellectual content. J.-H.Kang, K.-H.L., D.-W.K., S.-W.K., H.R.K., J.-H.Kim, J.-H.C., H..J.A., J.-S.K., J.-S.J., B.-S.K. and H.T.K.: designed, analysed and interpreted the data and approved the final paper.

Corresponding author

Correspondence to Heung Tae Kim.

Ethics declarations

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.

Data availability

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.

Competing interests

The authors declare no competing financial interests.

Funding information

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

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