Ribociclib with letrozole vs letrozole alone in elderly patients with hormone receptor-positive, HER2-negative breast cancer in the randomized MONALEESA-2 trial

Gabe S Sonke, Lowell L Hart, Mario Campone, Frans Erdkamp, Wolfgang Janni, Sunil Verma, Cristian Villanueva, Erik Jakobsen, Emilio Alba, Erik Wist, Anne M Favret, Thomas Bachelot, Roberto Hegg, Paul Wheatley-Price, Farida Souami, Santosh Sutradhar, Michelle Miller, Caroline Germa, Howard A Burris, Gabe S Sonke, Lowell L Hart, Mario Campone, Frans Erdkamp, Wolfgang Janni, Sunil Verma, Cristian Villanueva, Erik Jakobsen, Emilio Alba, Erik Wist, Anne M Favret, Thomas Bachelot, Roberto Hegg, Paul Wheatley-Price, Farida Souami, Santosh Sutradhar, Michelle Miller, Caroline Germa, Howard A Burris

Abstract

Purpose: Determine the efficacy and safety of first-line ribociclib plus letrozole in elderly patients with HR+, HER2- advanced breast cancer.

Methods: 668 postmenopausal women with HR+, HER2- advanced breast cancer and no prior systemic therapy for advanced disease were enrolled in the Phase III MONALEESA-2 trial (NCT01958021); 295 patients were aged ≥ 65 years. Patients were randomized to ribociclib (600 mg/day; 3-weeks-on/1-week-off) plus letrozole (2.5 mg/day) or placebo plus letrozole until disease progression, unacceptable toxicity, death, or treatment discontinuation. The primary endpoint was PFS, which was evaluated in elderly (≥ 65 years) and younger (< 65 years) patients. Secondary endpoints included response rates and safety.

Results: Ribociclib plus letrozole significantly improved PFS vs placebo plus letrozole in elderly (hazard ratio: 0.608; 95% CI 0.394-0.937) and younger patients (hazard ratio: 0.523; 95% CI 0.378-0.723). Overall response rates were numerically higher in the ribociclib vs placebo arm, regardless of age. Ribociclib plus letrozole was well tolerated in elderly patients, with the safety profile similar to the overall study population. Nausea, vomiting, alopecia, and diarrhea were > 10% more frequent in the ribociclib plus letrozole vs placebo plus letrozole arm in both subgroups; most events were grade 1/2. In elderly patients, grade 1/2 anemia and fatigue were > 10% more frequent in the ribociclib plus letrozole vs placebo plus letrozole arm and discontinuation rates were similar in both arms.

Conclusions: Addition of ribociclib to letrozole is a valid therapeutic option for elderly patients with HR+, HER2- advanced breast cancer in the first-line setting.

Keywords: Breast cancer; CDK inhibitor; Elderly; Endocrine therapy; Hormone receptor-positive; Ribociclib.

Conflict of interest statement

Conflict of interest

Dr. Sonke reports institutional reimbursement for steering committee activities from Novartis during the conduct of the study. Dr. Hart reports research funding to his institution. Prof. Campone reports fees for advisory boards from Novartis, during the conduct of the study; and fees for advisory boards from Lilly, Sanofi, Pfizer, and AstraZeneca outside the submitted work. Prof. Janni reports research grants and/or honoraria from Sanofi-Aventis, Novartis, Roche, Pfizer, AstraZeneca, Chugai, GSK, Eisai, Celgene, and Johnson & Johnson outside the submitted work. Dr. Alba reports grants from Roche outside the submitted work. Dr. Wist reports personal fees from Novartis for an advisory board and a lecture outside the submitted work. Dr. Bachelot reports grants, personal fees, and non-financial support from Roche, Novartis, and Pfizer and grants and personal fees from AstraZeneca outside the submitted work. Dr. Wheatley-Price reports advisory board fees from Novartis outside the submitted work. Ms. Souami, Dr. Miller, and Dr. Germa are employees of Novartis Pharmaceutical Corporation and hold Novartis stock options. Mr. Sutradhar is an employee of Novartis Pharmaceutical Corporation. Dr. Erdkamp, Dr. Verma, Dr. Villanueva, Dr. Jakobsen, Dr. Favret, Dr. Hegg, and Dr. Burris have nothing to disclose.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Figures

Fig. 1
Fig. 1
Trial profile (CONSORT diagram). CONSORT Consolidated Standards of Reporting Trials
Fig. 2
Fig. 2
Kaplan–Meier analysis of locally assessed PFS with ribociclib plus letrozole vs placebo plus letrozole in patients aged ≥65 years (a) and <65 years (b). CI confidence interval, HR hazard ratio, NR not reached, PFS progression-free survival

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Source: PubMed

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