Journal Article

Ribociclib plus Endocrine Therapy in Early Breast Cancer

Chakravartty, Arunava, Lipatov, Oleg, Nowecki, Zbigniew, Ghaznawi, Farhat, Severin, Irene, Hortobagyi, Gabriel, Stroyakovskiy, Daniil, Barrios, Carlos, Yardley, Denise A., Afenjar, Karen, McAndrew, Nicholas, Fresco, Rodrigo, Li, Zheng, Kukielka-Budny, Bozena, Hurvitz, Sara, Slamon, Dennis, Crown, John, Ji, Yan, Huang, Chiun-Sheng, Ruiz-Borrego, Manuel, Chia, Stephen, Loi, Sherene, Fasching, Peter A., Xu, Binghe, Taran, Tetiana, Bardia, Aditya, Untch, Michael, Im, Seock-Ah, Moroose, Rebecca, Visco, Frances, Zarate, Juan P.

2024

Overview

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. 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. 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. 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.).

• Publisher: Massachusetts Medical Society
• Subject: Aminopyridines - administration & dosage / Aminopyridines - adverse effects / Aminopyridines - therapeutic use / Anastrozole / Antineoplastic Agents, Hormonal / Antineoplastic Combined Chemotherapy Protocols - administration & dosage / Antineoplastic Combined Chemotherapy Protocols - adverse effects / Antineoplastic Combined Chemotherapy Protocols - therapeutic use / Aromatase / Aromatase Inhibitors - administration & dosage / Aromatase Inhibitors - adverse effects / Aromatase Inhibitors - therapeutic use / Breast Cancer / Breast Neoplasms - drug therapy / Breast Neoplasms - metabolism / Breast Neoplasms - mortality / Breast Neoplasms - pathology / Cancer therapies / Chemotherapy / Committees / Cyclin-dependent kinases / Design / Endocrine therapy / ErbB-2 protein / Female / Goserelin - administration & dosage / Goserelin - adverse effects / Goserelin - therapeutic use / Hematology / Humans / Hypothesis testing / Invasiveness / Kinases / Letrozole - administration & dosage / Letrozole - adverse effects / Letrozole - therapeutic use / Male / Oncology / Patients / Purines - administration & dosage / Purines - adverse effects / Purines - therapeutic use / Receptor, ErbB-2 - metabolism / Receptors, Estrogen / Receptors, Progesterone / Surgery / Survival / Targeted cancer therapy / Treatments in Oncology / Womens health