Final results of RIGHT Choice: Ribociclib plus endocrine therapy vs combination chemotherapy in premenopausal women with clinically aggressive HR+/HER2− advanced breast cancer
Mené sur 222 patientes atteintes d'un cancer du sein HR+ HER2- agressif de stade avancé, cet essai multicentrique randomisé de phase II compare l'efficacité, du point de vue de la survie sans progression, et la toxicité d'un doublet de chimiothérapie choisie par le médecin (docétaxel et capécitabine, paclitaxel et gemcitabine, capécitabine et vinorelbine) et du ribociclib en combinaison avec un traitement endocrinien de première ligne (létrozole/anastrozole et goséréline)
Purpose: A head-to-head comparison of efficacy between a cyclin-dependent kinase 4/6 inhibitor plus endocrine therapy (ET) versus combination chemotherapy (CT) has never been reported in patients with clinically aggressive hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2−) advanced breast cancer (ABC). Patients and Methods: In this open-label, multi-center, randomized phase 2 trial, pre/perimenopausal women with clinically aggressive HR+/HER2− ABC were randomized 1:1 to first-line ribociclib (600 mg daily; 3-weeks-on, 1-week-off) plus letrozole/anastrozole and goserelin or investigator’s choice of combination CT (docetaxel plus capecitabine, paclitaxel plus gemcitabine, or capecitabine plus vinorelbine). The primary endpoint was progression-free survival (PFS). Results: Among 222 patients randomized to ribociclib plus ET (n=112) or combination CT (n=110), 150 (67.6%) had symptomatic visceral metastases, 41 (18.5%) had rapid disease progression per investigator’s judgment, and 31 (14.0%) had symptomatic non-visceral disease. Overall, 106 (47.7%) patients had investigator-assessed visceral crisis. Median follow-up time was 37.0 months. At data cutoff, 31.3% (ribociclib arm) and 15.5% (CT arm) of patients had completed study treatment and transitioned to post-trial access. The median PFS was 21.8 months (ribociclib plus ET; 95% CI, 17.4-26.7 months) and 12.8 months (combination CT; 95% CI, 10.1-18.4 months); hazard ratio [HR], 0.61; 95% CI, 0.43-0.87; P=.003. The overall response rates and the median time to response in the ribociclib versus CT arms, respectively, were 66.1% and 61.8% and 4.9 months and 3.2 months (HR, 0.76; 95% CI, 0.55-1.06). Lower rates of symptomatic adverse events were observed in the ribociclib versus CT arm Conclusions: First-line ribociclib plus ET showed a significant PFS benefit, similar response rates, and better tolerability over combination CT in patients with clinically aggressive HR+/HER2− ABC.