来曲唑联合内分泌治疗早期乳腺癌。

Ribociclib plus Endocrine Therapy in Early Breast Cancer.

机构信息

From the David Geffen School of Medicine at the University of California, Los Angeles (D. Slamon, N.M.); Republican Clinical Oncology Dispensary, Ufa (O.L.), and Moscow City Oncology Hospital No. 62, Moscow (D. Stroyakovskiy) - both in Russia; Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw (Z.N.), and Centrum Onkologii Ziemi Lubelskiej im. św. Jana z Dukli, Lublin (B.K.-B.) - both in Poland; the Sarah Cannon Research Institute at Tennessee Oncology, Nashville (D.A.Y.); the National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei City (C.-S.H.); University Hospital Erlangen, the Comprehensive Cancer Center Erlangen-European Metropolitan Region of Nuremberg, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen (P.A.F.), and the Interdisciplinary Breast Cancer Center, Helios Klinikum Berlin-Buch, Berlin (M.U.) - both in Germany; St. Vincent's Hospital, Dublin (J.C.); Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston (A.B.); the British Columbia Cancer Agency, Vancouver (S.C.), and Translational Research in Oncology (TRIO), Edmonton, AB (I.S.) - both in Canada; the Cancer Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea (S.-A.I.); Hospital Virgen del Rocío, Seville, and Grupo Español de Investigación en Cáncer de Mama, Spanish Breast Cancer Group, Madrid - both in Spain (M.R.-B.); the Peter MacCallum Cancer Centre, Melbourne, VIC, Australia (S.L.); the Department of Medical Oncology Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (B.X.); the Fred Hutchinson Cancer Center, University of Washington, Seattle (S.H.); the Latin American Cooperative Oncology Group, Porto Alegre, Brazil (C.B.); the Orlando Health Cancer Institute, Orlando, FL (R.M.); the National Breast Cancer Coalition, Washington, DC (F.V.); TRIO, Paris (K.A.); TRIO, Montevideo, Uruguay (R.F.); Novartis Pharmaceuticals, East Hanover, NJ (Y.J., F.G., Z.L., J.P.Z., A.C.); Novartis Pharma, Basel, Switzerland (T.T.); and the Department of Breast Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston (G.H.).

出版信息

N Engl J Med. 2024 Mar 21;390(12):1080-1091. doi: 10.1056/NEJMoa2305488.

DOI:10.1056/NEJMoa2305488

PMID:38507751

Abstract

BACKGROUND

Ribociclib has been shown to have a significant overall survival benefit in patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. Whether this benefit in advanced breast cancer extends to early breast cancer is unclear.

METHODS

In this international, open-label, randomized, phase 3 trial, we randomly assigned patients with HR-positive, HER2-negative early breast cancer in a 1:1 ratio to receive ribociclib (at a dose of 400 mg per day for 3 weeks, followed by 1 week off, for 3 years) plus a nonsteroidal aromatase inhibitor (NSAI; letrozole at a dose of 2.5 mg per day or anastrozole at a dose of 1 mg per day for ≥5 years) or an NSAI alone. Premenopausal women and men also received goserelin every 28 days. Eligible patients had anatomical stage II or III breast cancer. Here we report the results of a prespecified interim analysis of invasive disease-free survival, the primary end point; other efficacy and safety results are also reported. Invasive disease-free survival was evaluated with the use of the Kaplan-Meier method. The statistical comparison was made with the use of a stratified log-rank test, with a protocol-specified stopping boundary of a one-sided P-value threshold of 0.0128 for superior efficacy.

RESULTS

As of the data-cutoff date for this prespecified interim analysis (January 11, 2023), a total of 426 patients had had invasive disease, recurrence, or death. A significant invasive disease-free survival benefit was seen with ribociclib plus an NSAI as compared with an NSAI alone. At 3 years, invasive disease-free survival was 90.4% with ribociclib plus an NSAI and 87.1% with an NSAI alone (hazard ratio for invasive disease, recurrence, or death, 0.75; 95% confidence interval, 0.62 to 0.91; P = 0.003). Secondary end points - distant disease-free survival and recurrence-free survival - also favored ribociclib plus an NSAI. The 3-year regimen of ribociclib at a 400-mg starting dose plus an NSAI was not associated with any new safety signals.

CONCLUSIONS

Ribociclib plus an NSAI significantly improved invasive disease-free survival among patients with HR-positive, HER2-negative stage II or III early breast cancer. (Funded by Novartis; NATALEE ClinicalTrials.gov number, NCT03701334.).

摘要

背景

在激素受体（HR）阳性、人表皮生长因子受体 2（HER2）阴性的晚期乳腺癌患者中，已证实瑞博西利具有显著的总生存获益。但该药在早期乳腺癌中的获益是否同样存在尚不清楚。

方法

在这项国际性、开放性、随机、3 期临床试验中，我们按照 1:1 的比例将 HR 阳性、HER2 阴性的早期乳腺癌患者随机分配，分别接受瑞博西利（剂量为 400 mg/天，连用 3 周，随后停药 1 周，连用 3 年）联合非甾体类芳香化酶抑制剂（NSAI；来曲唑 2.5 mg/天或阿那曲唑 1 mg/天，连用≥5 年）或 NSAI 单药治疗。绝经前女性和男性还每 28 天接受戈舍瑞林治疗。合格患者为解剖学分期为 II 期或 III 期的乳腺癌患者。本研究报告了预先设定的无侵袭性疾病生存期中止分析的结果，该分析是主要终点；同时也报告了其他疗效和安全性结果。无侵袭性疾病生存情况采用 Kaplan-Meier 法评估。统计学比较采用分层对数秩检验，采用方案规定的单侧 P 值阈值为 0.0128 的界值进行优效性检验。

结果

截至本次预先设定的中期分析截止日期（2023 年 1 月 11 日），共有 426 例患者发生侵袭性疾病、复发或死亡。与 NSAI 单药治疗相比，瑞博西利联合 NSAI 治疗显著改善了无侵袭性疾病生存情况。3 年时，瑞博西利联合 NSAI 组的无侵袭性疾病生存率为 90.4%，而 NSAI 单药组为 87.1%（侵袭性疾病、复发或死亡的风险比，0.75；95%置信区间，0.62 至 0.91；P=0.003）。次要终点——远处无疾病生存率和无复发生存率——也支持瑞博西利联合 NSAI。瑞博西利起始剂量为 400 mg 的 3 年治疗方案并未带来任何新的安全性信号。