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

Springer Science and Business Media LLC - Tập 189 Số 3 - Trang 689-699 - 2021
Michelino De Laurentiis1, Simona Borštnar2, Mario Campone3, Ellen Warner4, Javier Salvador Bofill5, William Jacot6, Susan Dent7, Miguel Martín8, Alistair Ring9, Paul Cottu10, Janice Lu11, Eva Ciruelos12, Hamdy A. Azim13, Sanjoy Chatterjee14, Katie Zhou15, Jiwen Wu15, Lakshmi Menon-Singh15, Claudio Zamagni16
1Division of Breast Medical Oncology, Department of Breast and Thoracic Oncology Director, Istituto Nazionale Tumori IRCCS "Fondazione Pascale", Napoli, Italy
2Institute of Oncology Ljubljana, Ljubljana, Slovenia
3Western Cancer Institute, Nantes, France
4Sunnybrook Health Sciences Centre, Toronto, ON, Canada
5Virgen del Rocío University Hospital, Biomedicine Institute, Seville, Spain
6Montpellier Cancer Institute, Montpellier, France
7The Ottawa Hospital Cancer Centre, Ottawa, ON, Canada
8Gregorio Marañón General University Hospital, GEICAM, Universidad Complutense, CIBERONC, Madrid, Spain
9Royal Marsden Hospital NHS Foundation Trust, Sutton, UK
10Curie Institute, Paris, France
11USC Norris Comprehensive Cancer Center, Los Angeles, CA, USA
12University Hospital 12 de Octubre, Clara Campal Comprehensive Cancer Center (HM CIOCC), Madrid, Spain
13Faculty of Medicine, Cairo University, Cairo, Egypt
14Tata Medical Center, Kolkata, India
15Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA
16Azienda Ospedaliero-Universitaria Di Bologna, Bologna, Italia

Tóm tắt

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.

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Springer Science and Business Media LLC

Tập 189 Số 3

689-699

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