PO.SHP01.01 · 科学与健康政策
Lurbinectedin联合atezolizumab与durvalumab维持治疗在ES-SCLC中的对比：临床与经济学分析
Lurbinectedin plus atezolizumab vs durvalumab maintenance in ES-SCLC: A comparative clinical and economic analysis
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
背景：广泛期小细胞肺癌（ES-SCLC）的治疗随着免疫治疗的加入而不断发展，生存获益不断改善。近期，IMforte试验报告了在诱导治疗后加用lurbinectedin联合atezolizumab维持治疗可带来更好的生存结局。这一方案对当前广泛使用的基于durvalumab的方案（CASPIAN试验）在ES-SCLC治疗中的地位构成了挑战。我们旨在分析这些方案的生存结局、毒性、耐受性和成本效益。
方法：IMforte和CASPIAN试验的数据直接从已发表的原始论文及其相关补充材料中提取，并进行描述性综合。生存结局，包括总生存期（OS）和无进展生存期（PFS），根据试验数据进行分析。对不良事件（AE）、耐受性以及采用每质量调整生命年（QALY）增量成本效益比（ICER）的成本效益进行了比较。
结果：在IMforte中，lurbinectedin联合atezolizumab维持治疗的中位OS为13.2个月，而atezolizumab为10.6个月（HR 0.73，p=0.017），PFS为5.4个月对2.1个月（HR 0.54，p<0.0001）。CASPIAN报告durvalumab的中位OS为12.9个月（对EP方案为10.5个月；HR 0.75，p=0.0032），PFS为5.1个月（对5.4个月；HR 0.80）。两项试验中的患者均接受了化疗联合免疫治疗的诱导。IMforte联合方案中3/4级AE更高（38%对22%），而CASPIAN试验各治疗组间的3/4级AE相似。IMforte试验显示更多骨髓抑制（如贫血8%、中性粒细胞减少7%），而CASPIAN则有更多免疫相关AE（20%对3%）。成本分析显示IMforte的ICER为1,071,238美元/QALY，而CASPIAN durvalumab为165,182美元/QALY，两者均超过150,000美元/QALY的阈值，但durvalumab更接近具有成本效益。经计算，我们机构的药物采购成本大约为：atezolizumab联合lurbinectedin（12个月）319,735美元，而durvalumab维持治疗（12个月）111,312美元。
结论：IMforte联合方案相较CASPIAN基于durvalumab的方案提供了更优的PFS和潜在更长的OS，但骨髓毒性增加且成本显著更高。CASPIAN方案更具成本效益，使其成为资源受限环境中可行的选择，且lurbinectedin可作为durvalumab进展后的后线治疗使用。IMforte试验不允许交叉，因此尚不清楚在ES-SCLC中早期引入lurbinectedin相比作为后续线治疗使用是否能带来更好的生存。这些发现为ES-SCLC的治疗选择提供了参考，在疗效、安全性和经济考量之间进行权衡。
查看英文原文 English abstract
Background Extensive-stage small cell lung cancer (ES-SCLC) treatment has evolved with improving survival with addition of immunotherapy treatment. Recently, the IMforte trial reported better survival outcomes by adding lurbectindin maintenance with atezolizumab after induction therapy. This approach challenges the current widely used durvalumab-based regimen (CASPIAN trial) for treatment of ES-SCLC. We aim to analyze the survival outcomes, toxicity, tolerability, and cost-effectiveness of these regimens.
Methods: Data from IMforte and CASPIAN trials were directly extracted from published primary manuscripts and associated supplementary materials and synthesized descriptively. Survival outcomes, including overall survival (OS) and progression-free survival (PFS), were analyzed from trial data. Adverse events (AEs), tolerability, and cost-effectiveness using the incremental cost-effectiveness ratio (ICER) per quality-adjusted life-year (QALY) were compared.
Results: In IMforte maintenance lurbinectedin plus atezolizumab yielded a median OS of 13.2 months vs. 10.6 months for atezolizumab (HR 0.73, p=0.017) and PFS of 5.4 months vs. 2.1 months (HR 0.54, p<0.0001). CASPIAN reported a median OS of 12.9 months with durvalumab (vs. 10.5 months for EP; HR 0.75, p=0.0032) and PFS of 5.1 months (vs. 5.4 months; HR 0.80). Patients in both trials received induction with a chemotherapy immunotherapy combination. Grade 3/4 AEs were higher in IMforte's combination (38% vs. 22%), and the CASPIAN trial reported similar grade 3/4 AEs between treatment arms. IMforte trial showed more myelosuppression (e.g., anemia 8%, neutropenia 7%) and CASPIAN more immune-related AEs (20% vs. 3%). Cost analysis revealed IMforte's ICER at $1,071,238/QALY versus CASPIAN durvalumab at $165,182/QALY, both exceeding the $150,000/QALY threshold but with durvalumab closer to cost-effectiveness. Our institutional drug acquisition cost was calculated to be $319,735 for atezolizumab plus lurbectinidin (12 months) vs $111,312 for duvalumab(12 months) maintenance, approximately.
Conclusions: The IMforte combination offers superior PFS and potentially longer OS than CASPIAN's durvalimab-based regimen, but with increased bone marrow toxicity and significantly higher costs. CASPIAN's regimen is more cost-effective, making it a viable option in resource-constrained settings, and lurbenectin can be used as a following line of treatment after progression on durvalumab. The IMforte trial did not allow a crossover; hence, it is unknown if early introduction of lurbecnectin for ES-SCLC will better survival rather than when used as a subsequent line treatment. These findings inform treatment selection for ES-SCLC, balancing efficacy, safety, and economic considerations.
利益披露 Disclosure
M. Krishnakumar, None..
S. Chennapragada, None..
A. Ashok, None..
A. Reddy, None.