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

Jin-Hyoung Kang, Ki-Hyeong Lee, Dong-Wan Kim, Sang-We Kim, Hye Ryun Kim, Joo-Hang Kim, Jin-Hyuk Choi, Ho Jung An, Jin-Soo Kim, Joung-Soon Jang, Bong-Seog Kim, Heung Tae Kim, Jin-Hyoung Kang, Ki-Hyeong Lee, Dong-Wan Kim, Sang-We Kim, Hye Ryun Kim, Joo-Hang Kim, Jin-Hyuk Choi, Ho Jung An, Jin-Soo Kim, Joung-Soon Jang, Bong-Seog Kim, Heung Tae Kim

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.

Trial registration: ClinicalTrials.gov NCT01497873.

Conflict of interest statement

The authors declare no competing financial interests.

Figures

Fig. 1. Waterfall plots demonstrating the efficacy…
Fig. 1. Waterfall plots demonstrating the efficacy of belotecan and topotecan monotherapy in patients with sensitive-relapsed SCLC.
Maximum percentage changes in tumour size (sum of the longest diameters of target-lesions) from baseline, in topotecan (a) and belotecan (b) groups. Colours indicate best overall responses determined from the start of treatment until disease progression/recurrence. p values were obtained from Chi-square tests for comparisons of ORR and DCR between groups.
Fig. 2. Survival curves for belotecan and…
Fig. 2. Survival curves for belotecan and topotecan.
Kaplan–Meier curves showing a PFS and b OS for belotecan and topotecan groups. p values were obtained from log-rank tests for comparisons of PFS and OS between groups. Vertical dashed line indicates 1-year OS rate. ORR objective response rate, DCR disease control rate, PFS progression-free disease, OS overall survival.
Fig. 3. Forest plot showing HR of…
Fig. 3. Forest plot showing HR of belotecan relative to topotecan for OS in different subgroups.
HR (95% CI) 

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Source: PubMed

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