萨曲珠单抗替瑞莫替康对比化疗治疗既往经治的局部复发或转移性三阴性乳腺癌：III期OptiTROP-Breast01研究的最终总生存期分析。
完整摘要 · 中文译文
背景：在3期OptiTROP-Breast01试验中，sacituzumab tirumotecan（sac-TMT）与化疗相比，显著改善了既往治疗过的晚期三阴性乳腺癌（TNBC）患者的无进展生存期，并且在预设的中期总生存期（OS）分析中观察到具有统计学显著性的总生存期获益。在此，我们报告延长随访后的最终总生存期分析。 患者与方法：总体而言，263例既往治疗过的局部复发或转移性TNBC患者按1:1随机分配至sac-TMT组（n=130）或化疗组（n=133）。总生存期是关键次要终点。 结果：在中位随访29.4个月时，sac-TMT组的中位总生存期为14.7个月（95% CI 12.1‒20.1），化疗组为9.9个月（95% CI 8.6‒11.8）（HR 0.60，95% CI 0.45‒0.80）；30个月总生存率分别为26.8%和13.2%。中期分析时观察到的总生存期获益在最终分析中得以维持，且在所有亚组中总体上一致。化疗组中有27.8%的患者接受了后续抗体药物偶联物（ADC）治疗。经使用秩保留结构失效时间模型对后续ADC治疗进行校正后，sac-TMT组的中位总生存期为14.7个月，化疗组估计为9.4个月（HR 0.55，95% CI 0.39‒0.73）；删失分析结果一致（HR 0.59，95% CI 0.43-0.82）。sac-TMT的安全性特征与既往结果保持一致，未出现新的安全信号。最常见的≥3级治疗相关不良事件为中性粒细胞计数降低、白细胞计数降低和贫血。 血症。探索性患者报告结局分析显示，与化疗相比，sac-TMT在所有五个评估的健康相关生活质量领域中的中位恶化时间均数值上更长，其中疲劳和疼痛领域的差异最大。结论：延长随访后的这些最终总生存期数据表明，sac-TMT相较于化疗具有临床意义且持续的OS获益，并进一步强化其作为既往经治晚期三阴性乳腺癌治疗选择的作用。未发现新的安全信号。
完整摘要 · 英文原文
BACKGROUND: In the phase 3 OptiTROP-Breast01 trial, sacituzumab tirumotecan (sac-TMT) significantly improved progression-free survival versus chemotherapy in patients with previously treated advanced triple-negative breast cancer (TNBC), with a statistically significant overall survival (OS) benefit observed at the prespecified interim OS analysis. Here we report the final OS analysis with extended follow-up. PATIENTS AND METHODS: Overall, 263 patients with previously treated locally recurrent or metastatic TNBC were randomly assigned 1:1 to sac-TMT (n=130) or chemotherapy (n=133). OS was a key secondary endpoint. RESULTS: At a median follow-up of 29.4 months, median OS was 14.7 months (95% CI 12.1‒20.1) with sac-TMT and 9.9 months (95% CI 8.6‒11.8) with chemotherapy (HR 0.60, 95% CI 0.45‒0.80); 30-month OS rates were 26.8% and 13.2%. The OS benefit observed at interim analysis was maintained at final analysis and generally consistent across all subgroups. Subsequent antibody-drug conjugate (ADC) therapy was received by 27.8% of patients in the chemotherapy group. After adjustment for subsequent ADC therapy using the rank-preserving structural failure time model, median OS was 14.7 months with sac-TMT and an estimated 9.4 months with chemotherapy (HR 0.55, 95% CI 0.39‒0.73); censoring analysis yielded consistent results (HR 0.59, 95% CI 0.43-0.82). The sac-TMT safety profile remained consistent with previous findings, with no new safety signals. The most common grade ≥3 treatment-related adverse events were decreased neutrophil count, decreased white blood cell count and anemia. Exploratory patient-reported outcome analyses showed numerically longer median time to deterioration with sac-TMT than with chemotherapy across all five evaluated health-related quality-of-life domains, with the largest differences for fatigue and pain. CONCLUSIONS: These final OS data after extended follow-up demonstrate a clinically meaningful and sustained OS benefit of sac-TMT versus chemotherapy and further reinforce its role as a treatment option for previously treated advanced TNBC. No new safety signals were identified.