Efficacy, safety, and prognosis prediction in patients treated with ribociclib in combination with letrozole: Final results of phase 3b RIBECCA study in hormone receptor positive, human epidermal growth factor receptor-2 negative, locally advanced or metastatic breast cancer.

BACKGROUND

In MONALEESA-2, addition of ribociclib to letrozole resulted in significantly longer progression-free survival (PFS) in postmenopausal women with HR+HER2- advanced breast cancer (ABC). RIBociclib for the treatment of advanCed breast CAncer (RIBECCA) study investigated ribociclib plus letrozole in a patient population reflecting routine clinical practice.

PATIENTS AND METHODS

In this multicenter, open-label, single-arm, phase 3b study, patients with HR+HER2- ABC not amenable to curative therapy and ECOG performance status ≤ 2 received ribociclib plus letrozole (cohort A: postmenopausal women and men in first-line; cohort B: pre-/perimenopausal women in first-line [B1], patients pretreated for advanced disease [B2]). The primary endpoint was clinical benefit rate (CBR) by week 24; secondary endpoints included overall response rate (ORR), PFS, overall survival (OS), and safety. Association of patient and tumor characteristics with PFS was analyzed by multivariable Cox regression analysis.

RESULTS

Overall, 487 patients were evaluable for efficacy, 502 for safety. By week 24, CBR was 60.8 % (95 % CI, 56.3-65.1), ORR was 19.3 % (95 % CI, 15.9-23.1). Median PFS was 21.8 months (95 % CI, 13.9-25.3) in first-line postmenopausal patients and 11.0 months (95 % CI, 8.2-16.4) in premenopausal and pretreated patients. Median OS was not reached. Higher baseline ECOG performance status, higher histological grade, and negative progesterone receptor status showed an unfavorable effect on PFS. Most common adverse events were neutropenia (50.0 %), nausea (42.0 %), and fatigue (39.2 %).

CONCLUSION

In this broad population of patients with HR+HER2- ABC, efficacy and safety results of ribociclib plus letrozole were similar to those observed in pivotal trials.

Informations de copyright

Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Peter A. Fasching reports personal fees from Novartis, grants from Biontech, grants and personal fees from Pfizer, personal fees from Daiichi-Sankyo, personal fees from Astra Zeneca, personal fees from Eisai, personal fees from Merck Sharp & Dohme, grants from Cepheid, personal fees from Lilly, personal fees from Pierre Fabre, personal fees from SeaGen, personal fees from Roche, personal fees from Hexal, personal fees from Agendia, personal fees from Sanofi Aventis, personal fees from Gilead, during the conduct of the study. Thomas Decker reports being on advisory board with Novartis, Lilly. Andreas Hartkopf reports consulting fees from Novartis, Pfizer, Lilly, MSD, AstraZeneca, Roche, Seattle Genetics, ExactSiences; honoraria from Novartis, Pfizer, Lilly, MSD, AstraZeneca, Roche; travel expenses from Roche, Pfizer, AstraZeneca; grants or contracts from ExactSiences; writing Support from Novartis. Arnd Nusch has no conflict of interest to disclose. Bernhard J. Heinrich has received documentation fees from Novartis. Christian M. Kurbacher received grants or contracts from Astra Zeneca, BMS, Eli Lilly, Immunomedics, MSD, Novartis, Pfizer, Riemser, Roche, Seattle Genetics; consulting fees from Amgen, Eli Lilly, Novartis, Pfizer, Riemser, Roche, GSK, Servier; honoraria from Amgen, Astra Zeneca, Clovis Oncology, Eli Lilly, MSD, Novartis, Pfizer, Roche, GSK; support for attending meetings and/or travel from Amgen, AstraZeneca, Immunomedics, Pfizer, TEVA Oncology; has been on advisory board with Amgen, Astra Zeneca, Eli Lilly, MSD, Novartis, Pfizer, Onkotrakt, PharmaMar, Riemser, Roche, GSK; has been on board of directors (unpaid) in Berufsverband niedergelassener gynäkologischer Onkologen in Deutschland e. V.(BNGO). Roswitha Fuchs has no conflict of interest to disclose. Hans Tesch has received consulting fees from Pierre Fabre, Pfizer Pharma, Mundipharma, ClinSol, Novartis, Lilly, Grünenthal, Vifor, AstraZeneca, Mylan, Amgen; honoraria from Vifor, Novartis, AstraZeneca, ClinSol, MundiPharma, Lilly, Amgen; travel expenses from Pierre Fabre, Pfizer, Mundipharma, ClinSol, Novartis, Lilly, Grünenthal, Vifor, AstraZeneca, Mylan, Amgen; has been on advisory board with Novartis, BMS, Molecular Health GmbH, AstraZeneca, Pfizer, Roche, Grünenthal, Mylan; has been in leadership or fiduciary role in Arbeitskreis KlinischeStudien e.V., ASCO, BNHO, DGHO, DKG, ESMO, Deutsche Ges. für Senologie. Petra Krabisch has no conflict of interest to disclose. Jens Huober reports research funding from Celgene, Novartis, Hexal; honoraria from Lilly, Novartis, Roche, Pfizer, AstraZeneca, MSD, Celgene, Eisai, Abbvie; consulting/advisory relationship with Lilly, Novartis, Roche, Pfizer, Hexal, AstraZeneca, MSD, Celgene, Abbvie; travel expenses from Roche, Pfizer, Novartis, Celgene, Daiichi. Sherko Kuemmel reports receiving consulting fees from Lilly, pfm medical, Somatex, MSD; honoraria from Roche, Genomic Health, Novartis, Amgen, Celgene, Daiichi Sankyo, AstraZeneca, Pfizer; travel expenses from Roche, Daiichi Sankyo, Lilly, Sonoscape; advisory board with Roche, Daiichi Sankyo, Lilly, MSD, AstraZeneca, Pfizer; leadership of fiduciary role in WSG (Co Director), AGO, NOGGOe.V, AGimed. Sara Y. Brucker reports receiving honoraria from Storz, Pfizer, Roche, Novartis, MSD, AstraZeneca; travel expenses from Storz, Pfizer, Roche, Novartis, MSD, AstraZeneca; advisory board with Storz, Pfizer, Roche, Novartis, MSD, AstraZeneca. Wolfgang Janni received grants or contracts from Novartis; consulting fees from Novartis; honoraria from Novartis; payment for expert testimony from Novartis; travel expenses from Novartis. Andreas Schneeweiss received writing support from Roche; grants or contracts from Celgene, Roche, AbbVie; consulting fees from Celgene, Pfizer, AstraZeneca, Novartis, MSD, Tesaro, Lilly; payment for expert testimony from Roche, AstraZeneca; travel expenses from Celgene, Roche, Pfizer. Martin Schuler reports receiving consultant fees from AstraZeneca, Boehringer Ingelheim, BMS, GSK, Janssen, Novartis, Roche, Takeda; honoraria from Amgen, Boehringer Ingelheim, BMS, Janssen, MSD, Novartis; research funding to institution from AstraZeneca, BMS. Tanja Fehm received honoraria from Roche, Novartis, Pfizer, Daiichi Sankyo, AstraZeneca, MSD, TEVA; travel expenses from Daiichi Sankyo, Roche; was on advisory board with Daiichi Sankyo, Roche, Pfizer.