Ribociclib plus letrozole in patients with hormone receptor‐positive, HER2‐negative advanced breast cancer with no prior endocrine therapy: subgroup analysis from the phase 3b CompLEEment‐1 trial

Subgroup analysis of the CompLEEment‐1 trial

Abstract

Background. First-line therapy with the CDK4/6 inhibitor, ribociclib, plus letrozole in combination with endocrine therapy significantly improved progression‐free survival in postmenopausal patients with HR+/HER2− advanced breast cancer (ABC) in a pivotal phase 3, placebo‐controlled trial (MONALEESA‐2) and demonstrated superior overall survival in premenopausal patients with HR+/HER2− ABC (MONALEESA‐7). The multinational, phase 3b, Com-pLEEment‐1 trial of ribociclib plus letrozole in a broader population of patients naïve to endocrine therapy for advanced disease is the largest phase 3 clinical trial to date to evaluate the safety and efficacy of a CDK4/6 inhibitor. We report a subanalysis of data from 339 patients enrolled in the central and south European countries of the SERCE (Southern Europe, RUC, Central Europe) cluster of CompLEEment‐1.

Patients and methods. Men and women of any menopausal status with HR+/HER2− ABC received once‐daily oral ribociclib 600 mg (3‐weeks on/1‐week‐off), plus letrozole 2.5 mg continuously. Men/premenopausal women also received a GnRH‐agonist. The primary outcome was the number of patients with adverse events (AEs) over a timeframe of approximately 36 months. Time‐to‐progression, overall response rate, and clinical benefit rate were also measured.

Results. Safety results in the SERCE subgroup were consistent with those in the pivotal clinical trials of ribociclib in combination with endocrine therapy. Treatment‐related AEs leading to dose adjustments/interruption occurred in 63.1% of patients but led to treatment discontinuation in only 10.6%. The most common treatment‐related AEs of grade ≥3 were neutropenia and transaminase elevations. There were no fatal treatment‐related events.

Conclusions. These findings from the SERCE subgroup support the safety and manageable tolerability of ribociclib in a broad range of patients with HR+/HER2− ABC more representative of patients in real‐world clinical practice.