Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer
Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer
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DOI：
10.1056/nejmoa1809615
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发表时间：
2018-11-29
影响因子：
158.5
通讯作者：
Emens, L. A.
中科院分区：
文献类型：
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作者：
Schmid, P.;Adams, S.;Emens, L. A.
背景可切除的局部晚期或转移性三阴性（激素受体阴性和人表皮生长因子受体2 [HER2]阴性）乳腺癌是一种预后差的侵袭性疾病。纳米颗粒白蛋白结合（nab）紫杉醇可能增强atezolizumab的抗癌活性。方法：在这项3期试验中，我们随机分配（以1:1的比例）未经治疗的转移性三阴性乳腺癌患者接受atezolizumab + nab-紫杉醇或安慰剂+ nab-紫杉醇；患者继续进行干预，直到疾病进展或出现不可接受的毒性作用。分层因素是接受或未接受新辅助或辅助紫杉醇治疗，基线时是否存在肝转移，以及基线时程序性死亡配体1 （PD-L1）表达（阳性与阴性）。两个主要终点是无进展生存期（在意向治疗人群和pd - l1阳性亚组中）和总生存期（在意向治疗人群中进行测试；如果发现显著，则将在pd - l1阳性亚组中进行测试）。结果每组纳入451例患者，中位随访时间12.9个月。在意向治疗分析中，atezolizumab + nab-紫杉醇组的中位无进展生存期为7.2个月，而安慰剂+ nab-紫杉醇组的中位无进展生存期为5.5个月（进展或死亡的风险比为0.80；95%可信区间[CI]， 0.69至0.92;P = 0.002）；pd - l1阳性肿瘤患者的中位无进展生存期分别为7.5个月和5.0个月(风险比为0.62；95% CI为0.49 ~ 0.78
BACKGROUNDUnresectable locally advanced or metastatic triple-negative (hormone-receptor-negative and human epidermal growth factor receptor 2 [HER2]-negative) breast cancer is an aggressive disease with poor outcomes. Nanoparticle albumin-bound (nab)paclitaxel may enhance the anticancer activity of atezolizumab.METHODSIn this phase 3 trial, we randomly assigned (in a 1: 1 ratio) patients with untreated metastatic triple-negative breast cancer to receive atezolizumab plus nab-paclitaxel or placebo plus nab-paclitaxel; patients continued the intervention until disease progression or an unacceptable level of toxic effects occurred. Stratification factors were the receipt or nonreceipt of neoadjuvant or adjuvant taxane therapy, the presence or absence of liver metastases at baseline, and programmed death ligand 1 (PD-L1) expression at baseline (positive vs. negative). The two primary end points were progression-free survival (in the intention-to-treat population and PD-L1-positive subgroup) and overall survival (tested in the intention-to-treat population; if the finding was significant, then it would be tested in the PD-L1-positive subgroup).RESULTSEach group included 451 patients (median follow-up, 12.9 months). In the intention-to-treat analysis, the median progression-free survival was 7.2 months with atezolizumab plus nab-paclitaxel, as compared with 5.5 months with placebo plus nab-paclitaxel (hazard ratio for progression or death, 0.80; 95% confidence interval [CI], 0.69 to 0.92; P = 0.002); among patients with PD-L1-positive tumors, the median progression-free survival was 7.5 months and 5.0 months, respectively (hazard ratio, 0.62; 95% CI, 0.49 to 0.78; P