A phase IV prospective study of efficacy and safety of ribociclib and letrozole as first-line therapy in older women (≥70 years) with hormone receptor-positive HER2-negative advanced breast cancer: the RibOB study.

BACKGROUND: Cyclin-dependent kinase 4/6 inhibitors with endocrine therapy are standard first-line therapy for patients with hormone receptor-positive metastatic breast cancer. Older patients, especially the frailer subpopulation, are underrepresented in clinical trials, limiting data on treatment and safety outcomes in this population. PATIENTS AND METHODS: The RibOB study was an open-label, single-arm phase IV prospective trial evaluating first-line ribociclib 600 mg 3 weeks out of 4 with letrozole in women ≥70 years with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer. Primary endpoint was progression-free survival (PFS). Secondary endpoints were safety, functional evolution and quality of life (QoL), and outcomes in relation to clinical frailty assessed by G8. RESULTS: Seventy patients were enrolled: median age 76 years, with 30% ≥80 years. Forty-five out of 70 patients had a G8 score of ≤14 (frail) at baseline. With a median follow-up of 30.5 months, the median PFS was 36 months (95% confidence interval 24 months-not estimable). Median overall survival rate was not reached and breast cancer-specific survival rate at 24 and 36 months was 82% and 75%, respectively. Median time to treatment failure was 14.6 months. There were no significant differences in efficacy between fit and frail patients. Forty-seven out of 70 patients (67%) had grade 3 or higher adverse events, most commonly neutropenia (47%). Liver toxicity grade 3 or higher occurred in 2/70 (3%), and grade 3 or higher QT prolongation in 3/70 (4%). Thirty out of 70 patients (43%) discontinued ribociclib before progression and 57% required dose reductions to 400 mg, and 23% to 200 mg. Only 14 patients (20%) continued with the full 600-mg dose until end of study, disease progression, or death. No significant change in mean QoL was observed over time. CONCLUSION: Ribociclib in combination with letrozole showed clear antitumor efficacy and safe treatment option in older patients with advanced breast cancer regardless of frailty. Frequent dose reductions and early discontinuation suggest the need for more research to optimize dosing in older patients.