Abstract
BackgroundThis study compared the efficacy/safety of the camptothecin analogues belotecan and topotecan for sensitive-relapsed small-cell lung cancer (SCLC).MethodsOne-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.ResultsIn 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).ConclusionsThe 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.
Highlights
This study compared the efficacy/safety of the camptothecin analogues belotecan and topotecan for sensitiverelapsed small-cell lung cancer (SCLC)
The primary endpoint was objective response rate (ORR), which is the percentage of patients with best overall response (OR) of complete response (CR) and partial response (PR)
The daily dose was reduced by 0.1 mg/m2 for belotecan and 0.25 mg/m2 for topotecan, if re-evaluation results showed any of the following: (1) absolute neutrophil count (ANC) between 1000–1500 per μL, (2) platelet count between 75,000 and 100,000 per μL, (3) febrile neutropenia amelioration, or (4) non-haematological grade 3/4 adverse event (AE) decreased to grade 1/2
Summary
Small-cell lung cancer (SCLC) is a highly aggressive carcinoma with early metastasis and poor prognosis, characterised by low differentiation, high mutational burden and high count of circulating tumour cells.[1]. The primary objective of this randomised clinical trial was to compare the efficacy and safety of topotecan vs belotecan as monotherapy for relapsed SCLC. The daily dose was reduced by 0.1 mg/m2 for belotecan and 0.25 mg/m2 for topotecan, if re-evaluation results showed any of the following: (1) ANC between 1000–1500 per μL, (2) platelet count between 75,000 and 100,000 per μL, (3) febrile neutropenia amelioration, or (4) non-haematological grade 3/4 AE decreased to grade 1/2. Discontinuation of clinical trial treatment Clinical trial treatment was terminated in the following circumstances: (1) symptomatic deterioration before completion of all six cycles of treatment, (2) more than two instances of treatment suspension or dose reduction, (3) patient’s voluntary withdrawal of consent, (4) protocol violation in enrolment, randomisation, or study compliance, (5) change to other treatments, (6) treating physician’s evaluation that the risks of AEs outweighed the benefits of treatment. Stratified Cox regression was used to compare topotecan and belotecan for PFS and OS in subgroup populations stratified by sex, age, time to relapse, baseline Hb, ECOG PS, disease stage, RDI, metastatic status and prior radiotherapy history
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