Full population results from the core phase of CompLEEment-1, a phase 3b study of ribociclib plus letrozole as first-line therapy for advanced breast cancer in an expanded population

Abstract

Purpose: CompLEEment-1 is a phase 3b trial in an expanded patient population with hormone receptor-positive (HR +), human epidermal growth factor receptor-2-negative (HER2-) advanced breast cancer (ABC), the largest current trial of cyclin-dependent kinase 4 and 6 inhibitors in ABC.

Methods: Patients treated with ≤ 1 line of prior chemotherapy and no prior endocrine therapy for ABC received ribociclib 600 mg/day (3-weeks-on/1-week-off) plus letrozole 2.5 mg/day and additionally monthly goserelin/leuprolide in men and pre-/perimenopausal women. Eligibility criteria allowed inclusion of patients with stable CNS metastases and an Eastern Cooperative Oncology Group performance status of 2. Primary objectives were safety and tolerability, and secondary objectives were efficacy and quality of life (QoL).

Results: Overall, 3,246 patients were evaluated (median follow-up 25.4 months). Rates of all-grade and grade ≥ 3 treatment-related adverse events (AEs) were 95.2% and 67.5%, respectively. Treatment-related discontinuations due to all grade and grade ≥ 3 AEs occurred in 12.9% and 7.3% of patients, respectively. Rates of all-grade AEs of special interest (AESI) were as follows: neutropenia (74.5%), increased alanine aminotransferase (16.2%), increased aspartate aminotransferase (14.1%), and QTcF prolongation (6.7%); corresponding values for grade ≥ 3 AESI were 57.2%, 7.7%, 5.7%, and 1.0%, respectively. Median time to progression was 27.1 months (95% confidence interval, 25.7 to not reached). Patient QoL was maintained during treatment.

Conclusion: Safety and efficacy data in this expanded population were consistent with the MONALEESA-2 and MONALEESA-7 trials and support the use of ribociclib plus letrozole in the first-line setting for patients with HR + , HER2- ABC.

Trial registration: linicalTrials.gov NCT02941926.

Keywords: Advanced breast cancer; CDK4/6 inhibitor; Endocrine therapy; Ribociclib.

Conflict of interest statement

Michelino De Laurentiis has received honoraria for consulting or advisory roles from Amgen, AstraZeneca, Celgene, Eisai, Lilly, MSD, Novartis, Pfizer, Pierre Fabre, and Roche; Honoraria: Amgen, AstraZeneca, Celgene, Eisai, Lilly, MSD, Novartis, Pfizer, Pierre Fabre, and Roche; honoraria for participation in speakers’ bureau from Novartis; research funding from Bristol-Myers Squibb, Daiichi Sankyo, Lilly, Novartis, MacroGenics, MSD, Pfizer, Puma Biotechnology, and Roche. Simona Borstnar has received honoraria for consulting or advisory roles from Amgen, AstraZeneca, Lilly, Novartis, Pfizer, and Roche; honoraria for participation in speakers’ bureaux from Amgen, Lilly, Krka, Novartis, Pfizer, and Roche. Mario Campone has received honoraria for consulting or advisory roles from AstraZeneca, Novartis, AbbVie, Sanofi, Lilly, Pfizer, Sandoz, Servier, Accord, and Pierre Fabre; honoraria from Novartis and Lilly; honoraria for participation in speakers’ bureaux from Novartis and Lilly; reimbursement for travel, accommodations, and expenses from Pfizer, Roche, and AstraZeneca. Ellen Warner has received reimbursement for travel, accommodations, or expenses from Novartis. Javier Salvador Bofill has received honoraria for consulting or advisory roles from Roche, Novartis, Pfizer, and MSD; honoraria for participation in speakers’ bureaux from Novartis and Roche; honoraria from Novartis, Pfizer, and Roche; reimbursement for travel, accommodations, or expenses from Roche, Novartis, and Pfizer. William Jacot has received honoraria for consulting or advisory roles from AstraZeneca, Eisai, Lilly France, MSD, Novartis, Pfizer, and Roche; research funding from AstraZeneca; reimbursement for travel, accommodations, or expenses from AstraZeneca, Chugai Pharma, Eisai, GlaxoSmithKline, and Lilly France. Susan Dent has received honoraria for consulting or advisory roles from Novartis, Pfizer, and Roche; honoraria from Eli Lilly, Novartis, and Roche; research funding from Hoffman La-Roche, Novartis, and Pfizer; reimbursement for travel, accommodations, or expenses from AstraZeneca. Miguel Martin has received honoraria for consulting or advisory roles from Amgen, AstraZeneca, Eli Lilly, Novartis, Pfizer, PharmaMar, Puma Biotechnology, Roche/Genentech, and Taiho Oncology; honoraria for participation in speakers’ bureaux from AstraZeneca, Amgen, Roche/Genentech, Novartis, and Pfizer; research funding from Roche and Novartis. Alistair Ring has received honoraria for consulting or advisory roles from Pfizer and Roche; honoraria from AstraZeneca, Lilly, Novartis, Pfizer, and Roche; research funding from AstraZeneca. Paul Cottu has received honoraria for consulting or advisory roles from Novartis and Pfizer; research funding from AstraZeneca, Genentech/Roche, Novartis, Pierre Fabre, and Pfizer; reimbursement for travel, accommodations, or expenses from AstraZeneca, NanoString Technologies, Novartis, Pfizer, and Roche. Janice Lu has received honoraria for consulting or advisory roles from Pfizer, Novartis, and Puma. Eva Ciruelos has received honoraria for consulting or advisory roles from Pfizer, Novartis, Lilly, and Roche; honoraria from Pfizer, Novartis, Lilly, and Roche; honoraria for participation in speakers’ bureaux from Pfizer, Novartis, Lilly, and Roche; reimbursement for travel, accommodations, or expenses from Pfizer and Roche. Hamdy A. Azim has received honoraria for consulting or advisory roles from ASZ, Bristol-Myers Squibb, Janssen, MSD, Novartis, Pfizer, Amgen, Lilly, and Roche; employment by Innate France (immediate family member); honoraria from Amgen, ASZ, Bristol-Myers Squibb, MSD, Novartis, Pfizer, and Roche; research funding from Pfizer. Sanjoy Chatterjee has received honoraria for consulting or advisory roles from Tata Medical Center. Katie Zhou is employed by Novartis. Jiwen Wu is employed by Novartis. Lakshmi Menon-Singh is employed by Novartis. Claudio Zamagni has received honoraria for consulting or advisory roles from AstraZeneca, Eisai, Novartis, Pfizer, PharmaMar, Pierre Fabre, and Roche; research funding from AbbVie, Array BioPharma, AstraZeneca, Celgene, Medivation, Morphotek, Novartis, Pfizer, Roche, and Roche/Genentech; reimbursement for travel, accommodations, or expenses from Celgene, Novartis, Pierre Fabre, and Roche.

© 2021. The Author(s).

Figures

Fig. 1

Kaplan–Meier plot of time to progression per local investigator assessment (full analysis set). CI confidence interval, NR not reached