First-line atezolizumab plus nab-paclitaxel for unresectable, locally advanced, or metastatic triple-negative breast cancer: IMpassion130 final overall survival analysis
First-line atezolizumab plus nab-paclitaxel for unresectable, locally advanced, or metastatic triple-negative breast cancer: IMpassion130 final overall survival analysis
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DOI：
10.1016/j.annonc.2021.05.355
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发表时间：
2021-07-13
影响因子：
50.5
通讯作者：
Schmid, P.
中科院分区：
文献类型：
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作者：
Emens, L. A.;Adams, S.;Schmid, P.
背景：基于IMpassion130，指南推荐atezolizumab联合nab-紫杉醇（A + nP）一线治疗肿瘤浸润免疫细胞（IC）表达程序性死亡配体1 （PD-L1）的不可切除、局部晚期或转移性三阴性乳腺癌。我们根据预先指定的分析计划报告该研究的最终总生存期（OS）和安全性。患者和方法：患者随机接受nP 100mg /m(2)（28天周期的第1、8和15天），atezolizumab 840 mg （a + nP）或安慰剂（P + nP；第1和15天），直到进展或不可接受的毒性。主要终点是无进展生存期[意向治疗（ITT）和PD-L1 ic阳性人群]和OS（在ITT人群中分层测试，如果有意义，在PD-L1 ic阳性人群中测试）。结果：每组451例；截至最终OS分析截止，666例（73.8%）死亡（中位随访18.8个月，四分位数范围8.9-34.7个月）。ITT人群的中位OS为A + nP组的21.0个月[95%可信区间（CI）， 19.0 ~ 23.4个月]，P + nP组的中位OS为18.7个月（95% CI, 16.9 ~ 20.8个月）[分层风险比（HR）， 0.87；95% ci, 0.75-1.02；P = 0.077]。对PD-L1 ic阳性人群的探索性分析显示，a + nP组（n = 185）的中位OS为25.4个月（95% CI, 19.6-30.7个月），P + nP组（n = 184）的中位OS为17.9个月（95% CI, 13.6-20.3个月），分层HR为0.67;95% CI, 0.53-0.86)。安全性结果与先前的分析和每种药物已知的毒性特征一致。在接受A + nP和P + nP治疗的患者中，分别有58.7%和41.6%的患者报告了免疫介导的特殊不良事件。结论：尽管ITT人群的OS获益没有统计学意义，排除了正式测试，但在PD-L1 ic阳性患者中观察到A + nP有临床意义的OS获益，与先前的中期分析一致。在更长时间的随访中，这种组合仍然是安全且耐受的。
Background: Guidelines recommend atezolizumab plus nab-paclitaxel (A + nP) for first-line treatment of unresectable, locally advanced, or metastatic triple-negative breast cancer expressing programmed death-ligand 1 (PD-L1) on tumor infiltrating immune cells (IC), based on IMpassion130. We report the final overall survival (OS) and safety of that study as per the prespecified analysis plan.Patients and methods: Patients were randomized to nP 100 mg/m(2) (days 1, 8, and 15 of a 28-day cycle) with atezolizumab 840 mg (A + nP) or placebo (P + nP; days 1 and 15), until progression or unacceptable toxicity. Coprimary endpoints were progression-free survival [intention-to-treat (ITT) and PD-L1 IC-positive populations] and OS (tested hierarchically in the ITT population and, if significant, in the PD-L1 IC-positive population).Results: Each arm comprised 451 patients; 666 (73.8%) had died by the final OS analysis cut-off (median follow-up, 18.8 months; interquartile range, 8.9-34.7 months). Median OS in the ITT population was 21.0 months [95% confidence interval (CI), 19.0-23.4 months] with A + nP, and 18.7 months (95% CI, 16.9-20.8 months) with P + nP [stratified hazard ratio (HR), 0.87; 95% CI, 0.75-1.02; P = 0.077]. Exploratory analysis in the PD-L1 IC-positive population showed a median OS of 25.4 months (95% CI, 19.6-30.7 months) with A + nP (n = 185) and 17.9 months (95% CI, 13.6-20.3 months) with P + nP (n = 184; stratified HR, 0.67; 95% CI, 0.53-0.86). Safety outcomes were consistent with previous analyses and the known toxicity profiles of each agent. Immune-mediated adverse events of special interest were reported in 58.7% and 41.6% of patients treated with A + nP and P + nP, respectively.Conclusion: Although the OS benefit in the ITT population was not statistically significant, precluding formal testing, clinically meaningful OS benefit was observed with A + nP in PD-L1 IC-positive patients, consistent with prior interim analyses. This combination remained safe and tolerable with longer follow-up.