Objectives

This report focuses on lurbinectedin activity and safety in a subgroup of small cell lung cancer (SCLC) patients from a Basket phase 2 study (Trigo et al. Lancet Oncology 2020;21:645–654) with chemotherapy-free interval (CTFI) ≥ 30 days. This pre-planned analysis was requested for obtaining regulatory approval of lurbinectedin in Switzerland.

Materials and methods

Patients with extensive-stage SCLC, no central nervous system (CNS) metastases, and disease progression after platinum-containing therapy were included. Topotecan data from a contemporary, randomized, controlled phase 3 study (ATLANTIS) were used as indirect external control in a matched patient population (n = 98 patients).

Results

Lurbinectedin showed a statistically significant higher overall response rate (ORR) by investigator assessment (IA) compared to topotecan subgroup (41.0 % vs. 25.5 %; p = 0.0382); higher ORR by Independent Review Committee (IRC) (33.7 % vs. 25.5 %); longer median duration of response (IA: 5.3 vs. 3.9 months; IRC: 5.1 vs. 4.3 months), and longer median overall survival (10.2 vs. 7.6 months). Grade ≥ 3 hematological abnormalities were remarkably lower with lurbinectedin: anemia 12.0 % vs. 54.1 %; leukopenia 30.1 % vs. 68.4 %; neutropenia 47.0 % vs. 75.5 %, and thrombocytopenia 6.0 % vs. 52.0 %. Febrile neutropenia was observed at a higher incidence with topotecan (6.1 % vs. 2.4 % with lurbinectedin) despite that the use of growth-colony stimulating factors was mandatory with topotecan.

Conclusion

With the limitations of an indirect comparison, however using recent and comparable SCLC datasets, this post hoc analysis shows that SCLC patients with CTFI ≥ 30 days and no CNS metastases have a positive benefit/risk ratio with lurbinectedin, superior to that observed with topotecan.

中文翻译：

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Lurbinectedin治疗无化疗间隔≥30天且无中枢神经转移的小细胞肺癌患者

目标

本报告重点关注来自 Basket 2 期研究（Trigo等人，Lancet Oncology 2020；21：645–654）的无化疗间隔 (CTFI) ≥的小细胞肺癌 (SCLC) 患者亚组中 lurbinectedin 的活性和安全性30天。这项预先计划的分析是为了获得 lurbinectedin 在瑞士的监管批准。

材料和方法

包括广泛期 SCLC、无中枢神经系统 (CNS) 转移且含铂治疗后疾病进展的患者。来自当代随机对照 3 期研究 (ATLANTIS) 的拓扑替康数据被用作匹配患者群体（n = 98 名患者）的间接外部对照。

结果

根据研究者评估 (IA)，与拓扑替康亚组相比，Lurbinectedin 显示出统计学上显着更高的总体缓解率 (ORR)（41.0 % vs. 25.5 %；p = 0.0382）；独立审查委员会 (IRC) 的 ORR 更高（33.7 %对比25.5 %）；中位缓解持续时间更长（IA：5.3 个月与3.9 个月；IRC：5.1 个月与4.3 个月），中位总生存期更长（10.2 个月与7.6 个月）。lurbinectedin 组 ≥ 3 级血液学异常显着降低：贫血 12.0 % vs. 54.1 %；白细胞减少症 30.1 %对比68.4 %；中性粒细胞减少症 47.0% vs. 75.5%，血小板减少症 6.0% vs. 52.0%。尽管拓扑替康强制使用生长集落刺激因子，但拓扑替康组观察到发热性中性粒细胞减少症的发生率较高（6.1% vs.鲁比奈丁组 2.4%）。

结论

然而，由于间接比较的局限性，使用最近和可比较的 SCLC 数据集，这项事后分析表明，CTFI ≥ 30 天且无 CNS 转移的 SCLC 患者使用 lurbinectedin 具有积极的获益/风险比，优于使用拓扑替康观察到的结果。