Overall Survival with Ribociclib plus Endocrine Therapy in Breast Cancer
Overall Survival with Ribociclib plus Endocrine Therapy in Breast Cancer
复制标题
DOI：
10.1056/nejmoa1903765
复制
发表时间：
2019-07-25
影响因子：
158.5
通讯作者：
Tripathy, D.
中科院分区：
文献类型：
--
作者：
Im, S. -A.;Lu, Y. -S.;Tripathy, D.
前期的一项3期试验分析显示，在绝经前或围绝经期晚期激素受体阳性、人表皮生长因子受体2 （HER2）阴性乳腺癌患者中，在内分泌治疗中加入细胞周期蛋白依赖性激酶4和6 （CDK4/6）抑制剂比单独使用内分泌治疗更有利于无进展生存。在这里，我们报告了一项协议指定的关键次要终点总生存期的中期分析结果。方法：我们随机分配患者在接受内分泌治疗（戈舍林和非甾体芳香化酶抑制剂或他莫昔芬）的基础上接受核波西尼或安慰剂。使用分层对数秩检验评估总生存期，并使用Kaplan-Meier方法进行总结。结果共有672例患者纳入意向治疗人群。335例患者中有83例死亡（24.8%），337例患者中有109例死亡（32.3%）。与单独的内分泌治疗相比，在内分泌治疗中加入核糖环尼可显著延长总生存期。估计42个月时，核素西尼组的总生存率为70.2%(95%可信区间[CI]， 63.5至76.0)，安慰剂组为46.0% (95% CI， 32.0至58.9)（死亡风险比为0.71;95% CI， 0.54至0.95；log-rank检验P=0.00973）。495名接受芳香酶抑制剂治疗的亚组患者的生存获益与总体意向治疗人群的生存获益一致（死亡风险比为0.70；95% CI为0.50至0.98）。随后接受抗肿瘤治疗的患者比例在两组之间是平衡的（核素昔尼组为68.9%，安慰剂组为73.2%）。在接受二线治疗期间，从随机分配到疾病进展或死亡的时间，核素昔尼组也比安慰剂组更长（疾病进展或死亡的风险比，0.69;95% CI， 0.55至0.87）。结论：该试验显示，在晚期激素受体阳性her2阴性乳腺癌患者中，CDK4/6抑制剂联合内分泌治疗的总生存期明显长于单独内分泌治疗。在较长时间的随访中，没有出现关于毒性作用的新担忧。
BackgroundAn earlier analysis of this phase 3 trial showed that the addition of a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor to endocrine therapy provided a greater benefit with regard to progression-free survival than endocrine therapy alone in premenopausal or perimenopausal patients with advanced hormone-receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Here we report the results of a protocol-specified interim analysis of the key secondary end point of overall survival.MethodsWe randomly assigned patients to receive either ribociclib or placebo in addition to endocrine therapy (goserelin and either a nonsteroidal aromatase inhibitor or tamoxifen). Overall survival was evaluated with the use of a stratified log-rank test and summarized with the use of Kaplan-Meier methods.ResultsA total of 672 patients were included in the intention-to-treat population. There were 83 deaths among 335 patients (24.8%) in the ribociclib group and 109 deaths among 337 patients (32.3%) in the placebo group. The addition of ribociclib to endocrine therapy resulted in significantly longer overall survival than endocrine therapy alone. The estimated overall survival at 42 months was 70.2% (95% confidence interval [CI], 63.5 to 76.0) in the ribociclib group and 46.0% (95% CI, 32.0 to 58.9) in the placebo group (hazard ratio for death, 0.71; 95% CI, 0.54 to 0.95; P=0.00973 by log-rank test). The survival benefit seen in the subgroup of 495 patients who received an aromatase inhibitor was consistent with that in the overall intention-to-treat population (hazard ratio for death, 0.70; 95% CI, 0.50 to 0.98). The percentage of patients who received subsequent antineoplastic therapy was balanced between the groups (68.9% in the ribociclib group and 73.2% in the placebo group). The time from randomization to disease progression during receipt of second-line therapy or to death was also longer in the ribociclib group than in the placebo group (hazard ratio for disease progression or death, 0.69; 95% CI, 0.55 to 0.87).ConclusionsThis trial showed significantly longer overall survival with a CDK4/6 inhibitor plus endocrine therapy than with endocrine therapy alone among patients with advanced hormone-receptor-positive, HER2-negative breast cancer. No new concerns regarding toxic effects emerged with longer follow-up.