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瑞博西林联合来曲唑治疗晚期乳腺癌的总生存期。

Overall Survival with Ribociclib plus Letrozole in Advanced Breast Cancer.

机构信息

From the Department of Breast Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston (G.N.H.), and Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center (C.L.A.), and Baylor University Medical Center, Texas Oncology, US Oncology (J.O.), Dallas - all in Texas; the Institute of Oncology, Davidoff Center, Rabin Medical Center, Tel Aviv University, Tel Aviv, Israel (S.M.S.); Sarah Cannon Research Institute, Nashville (H.A.B.); the Department of Medical Oncology, National Cancer Centre Singapore, Singapore (Y.-S.Y.); the Department of Medical Oncology, Netherlands Cancer Institute and Borstkanker Onderzoek Groep Study Center, Amsterdam (G.S.S.); Florida Cancer Specialists, Sarah Cannon Research Institute, Fort Myers (L.H.); the Department of Medical Oncology, Institut de Cancérologie de l'Ouest-René Gauducheau, Saint-Herblain (M.C.), and the Department of Medical Oncology, Institut Gustave Roussy, Medical School, Université Paris-Saclay, Villejuif (F.A.) - both in France; the Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Brno, Czech Republic (K.P.); the Department of Medical Oncology, Dana-Farber Cancer Institute, Boston (E.P.W.); the Department of Gynecology, University of Ulm, Ulm, Germany (W.J.); the Department of Surgery, Oncology, and Gastroenterology, University of Padua, and the Division of Medical Oncology 2, Istituto Oncologico Veneto, IRCCS, Padua, Italy (P.C.); the Edinburgh Cancer Research Centre, Institute of Genomics and Cancer, University of Edinburgh, Edinburgh (D.A.C.); Novartis Pharmaceuticals, East Hanover, NJ (J.P.Z., A.C.); and Novartis Pharma, Basel, Switzerland (T.T., F.L.G., P.S.).

出版信息

N Engl J Med. 2022 Mar 10;386(10):942-950. doi: 10.1056/NEJMoa2114663.

DOI:10.1056/NEJMoa2114663

PMID:35263519

Abstract

BACKGROUND

In a previous analysis of this phase 3 trial, first-line ribociclib plus letrozole resulted in significantly longer progression-free survival than letrozole alone among postmenopausal patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. Whether overall survival would also be longer with ribociclib was not known.

METHODS

Here we report the results of the protocol-specified final analysis of overall survival, a key secondary end point. Patients were randomly assigned in a 1:1 ratio to receive either ribociclib or placebo in combination with letrozole. Overall survival was assessed with the use of a stratified log-rank test and summarized with the use of Kaplan-Meier methods after 400 deaths had occurred. A hierarchical testing strategy was used for the analysis of progression-free survival and overall survival to ensure the validity of the findings.

RESULTS

After a median follow-up of 6.6 years, 181 deaths had occurred among 334 patients (54.2%) in the ribociclib group and 219 among 334 (65.6%) in the placebo group. Ribociclib plus letrozole showed a significant overall survival benefit as compared with placebo plus letrozole. Median overall survival was 63.9 months (95% confidence interval [CI], 52.4 to 71.0) with ribociclib plus letrozole and 51.4 months (95% CI, 47.2 to 59.7) with placebo plus letrozole (hazard ratio for death, 0.76; 95% CI, 0.63 to 0.93; two-sided P = 0.008). No new safety signals were observed.

CONCLUSIONS

First-line therapy with ribociclib plus letrozole showed a significant overall survival benefit as compared with placebo plus letrozole in patients with HR-positive, HER2-negative advanced breast cancer. Median overall survival was more than 12 months longer with ribociclib than with placebo. (Funded by Novartis; MONALEESA-2 ClinicalTrials.gov number, NCT01958021.).

摘要

背景

在这项 3 期试验的之前分析中，一线使用瑞博西利联合来曲唑治疗相比于单独使用来曲唑，可显著延长绝经后激素受体（HR）阳性、人表皮生长因子受体 2（HER2）阴性晚期乳腺癌患者的无进展生存期。瑞博西利是否也能延长总生存期尚不清楚。

方法

本研究报告了该试验方案规定的总生存期的最终分析结果，这是一个关键次要终点。患者以 1:1 的比例随机分配，分别接受瑞博西利或安慰剂联合来曲唑治疗。采用分层对数秩检验评估总生存期，并在发生 400 例死亡后采用 Kaplan-Meier 方法进行总结。采用分层检验策略分析无进展生存期和总生存期，以确保结果的有效性。

结果

中位随访 6.6 年后，瑞博西利组 334 例患者中有 181 例（54.2%）死亡，安慰剂组 334 例患者中有 219 例（65.6%）死亡。瑞博西利联合来曲唑与安慰剂联合来曲唑相比，具有显著的总生存期获益。瑞博西利联合来曲唑的中位总生存期为 63.9 个月（95%置信区间[CI]，52.4 至 71.0），安慰剂联合来曲唑的中位总生存期为 51.4 个月（95%CI，47.2 至 59.7）（死亡风险比，0.76；95%CI，0.63 至 0.93；双侧 P=0.008）。未观察到新的安全性信号。