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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

British Journal of Cancer volume 124, pages713–720(2021)Cite this article

Subjects

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

  1. The Catholic University of Korea Seoul St. Mary’s Hospital, Seoul, South Korea

    Jin-Hyoung Kang

  2. Chungbuk National University Hospital, Cheongju, South Korea

    Ki-Hyeong Lee

  3. Seoul National University Hospital, Seoul, South Korea

    Dong-Wan Kim

  4. Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea

    Sang-We Kim

  5. Yonsei Cancer Center, Division of Medical Oncology, Yonsei University College of Medicine, Seoul, South Korea

    Hye Ryun Kim

  6. CHA University Bundang Medical Center, Seongnam, South Korea

    Joo-Hang Kim

  7. Ajou University Hospital, Suwon, South Korea

    Jin-Hyuk Choi

  8. The Catholic University of Korea St. Vincent’s Hospital, Seoul, South Korea

    Ho Jung An

  9. Seoul National University Boramae Medical Center, Seoul, South Korea

    Jin-Soo Kim

  10. Chung-Ang University College of Medicine, Seoul, South Korea

    Joung-Soon Jang

  11. Veterans Health Service Medical Center, Seoul, South Korea

    Bong-Seog Kim

  12. National Cancer Center, Goyang, South Korea

    Heung Tae Kim

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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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Note This work is published under the standard license to publish agreement. After 12 months the work will become freely available and the license terms will switch to a Creative Commons Attribution 4.0 International (CC BY 4.0).

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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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