Background: Docetaxel is the standard of care for advanced non-small cell lung cancer (NSCLC) after platinum-based chemotherapy and/or immunotherapy but is associated with modest clinical outcomes and considerable toxicity. Sacituzumab govitecan and datopotamab deruxtecan are trophoblast cell surface antigen (TROP)-2-directed antibody–drug conjugates (ADCs) that showed encouraging activity in pretreated patients with advanced NSCLC. This systematic review and pooled analysis aims to comprehensively assess the efficacy and safety of anti-TROP-2 ADCs compared to docetaxel in pretreated patients with advanced NSCLC. Methods: A systematic search through PubMed and EMBASE before 31 January 2025 was performed to identify eligible studies. Randomized controlled phase III trials comparing an anti-TROP-2 regimen to docetaxel in patients with pretreated advanced NSCLC were included. Overall survival (OS), progression-free survival (PFS), and grade ≥ 3 treatment-related adverse events (TRAEs) were extracted from the identified trials. A pooled analysis of reconstructed patient data and meta-analysis employing the random-effect model were used to summarize the efficacy and safety outcomes. Results: Across the two trials included, 1207 patients were enrolled, 598 in the TROP-2 ADC arm and 609 in the docetaxel arm. Anti-TROP-2 treatment did not produce significant improvements in OS (HR: 0.90; 95% CI, 0.78–1.03; P = 0.13) and PFS (HR: 0.84; 95% CI, 0.68–1.02; P = 0.08), compared to docetaxel, even in patients with a nonsquamous histology (OS HR: 0.86; 95% CI, 0.73–1.01; P = 0.06; PFS HR: 0.76; 95% CI, 0.52–1.12; P = 0.17). Across the subgroup analyses, a statistically significant improvement in OS was observed in patients with actionable genomic alterations (AGAs) (HR: 0.63; 95% CI, 0.41–0.95; P = 0.03). Compared to docetaxel, the anti-TROP-2 regimen demonstrated a lower risk of developing grade ≥ 3 TRAEs (RR: 0.76; 95% CI, 0.55–1.05; P = 0.09). Conclusions: The anti-TROP-2 regimen showed a better safety profile but failed to demonstrate a relevant clinical improvement over docetaxel. Anti-TROP-2 ADCs could find a role in the management of patients with AGAs.
背景：多西他赛是晚期非小细胞肺癌（NSCLC）患者接受铂类化疗和/或免疫治疗后的标准治疗，但其临床疗效有限且毒性显著。戈沙妥珠单抗与德达托妥单抗是靶向滋养层细胞表面抗原（TROP-2）的抗体偶联药物（ADCs），在经治晚期NSCLC患者中显示出令人鼓舞的活性。本系统综述与汇总分析旨在全面评估抗TROP-2 ADCs对比多西他赛在经治晚期NSCLC患者中的疗效与安全性。 方法：系统检索截至2025年1月31日的PubMed和EMBASE数据库，筛选符合条件的研究。纳入在经治晚期NSCLC患者中比较抗TROP-2方案与多西他赛的随机对照III期试验。从纳入试验中提取总生存期（OS）、无进展生存期（PFS）及≥3级治疗相关不良事件（TRAEs）数据。采用随机效应模型对重建的患者数据进行汇总分析和Meta分析，以综合评估疗效与安全性结局。 结果：两项纳入试验共招募1207例患者，其中抗TROP-2 ADC组598例，多西他赛组609例。与多西他赛相比，抗TROP-2治疗未显著改善OS（风险比[HR]：0.90；95%置信区间[CI]，0.78–1.03；P=0.13）和PFS（HR：0.84；95% CI，0.68–1.02；P=0.08），即使在非鳞状组织学亚组中亦如此（OS HR：0.86；95% CI，0.73–1.01；P=0.06；PFS HR：0.76；95% CI，0.52–1.12；P=0.17）。在亚组分析中，具有可作用基因组改变（AGAs）的患者观察到OS有统计学意义的显著改善（HR：0.63；95% CI，0.41–0.95；P=0.03）。与多西他赛相比，抗TROP-2方案发生≥3级TRAEs的风险更低（相对风险[RR]：0.76；95% CI，0.55–1.05；P=0.09）。 结论：抗TROP-2方案显示出更好的安全性，但未能证明其临床疗效优于多西他赛。抗TROP-2 ADCs可能在治疗具有AGAs的患者中具有一定应用价值。
肿瘤(癌症)患者之家