Abstract PS10-49: Phase 3b CompLEEment-1 study of ribociclib plus letrozole in the treatment of HR+/HER2- advanced breast cancer: Final results from the UK cohort
Authors: Tuthill Mark , Marwaha Hardeep , Hartmann Christoph EA 
Published: February 2021

Background: Ribociclib is an oral selective CDK4/6 inhibitor approved for use in combination with an aromatase inhibitor (AI) or fulvestrant, in women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) in several countries, including the UK. Ribociclib plus endocrine therapy (ET) significantly improved PFS outcomes in phase III registration studies (MONALEESA-2, -3, and-7) compared with placebo plus ET; and significantly increased OS in combination with AI in premenopausal women (MONALEESA-7), and in combination with fulvestrant in postmenopausal women (MONALEESA-3). This analysis aims to report the final efficacy and safety results for the UK cohort of CompLEEment-1, a phase 3b trial evaluating ribociclib plus letrozole in an expanded patient population.Methods: Patients with HR+, HER2- ABC, ≤1 line of prior chemotherapy (CT), and no prior ET in the advanced setting, received ribociclib + letrozole. Baseline characteristics and interim results of the UK cohort have been reported previously (Ring et al. SABCS 2019. Poster 443).Results: A total of 139 UK patients received ≥1 dose of study treatment at UK sites. At the cut-off date, November 8th 2019, 53 patients (38.1%) had completed treatment and 86 discontinued due to disease progression (30.9%), adverse events (24.5%), physician or subject/guardian decision (2.9% each), and protocol deviation (0.7%). The mean age of patients was 61.3 (SD10.67). 138 (99.3%) patients were female, 125 (89.9%) were post-menopausal and 50 (35.9%) had an ECOG status of ≥1. 85 (61.1%) patients had received prior chemotherapy in any setting.89 (64.0%) patients had measurable disease at baseline. 80 (60.4%) patients presented with visceral disease, 35 (25.2%) with bone-only metastases and 4 (2.9%) had CNS metastases. 59 (42.5%) of patients had ≥3 metastatic sites. The median duration of exposure to study treatment was 18.4 months with a median time to progression of 27.6 months. The overall response rate was 25.9% (95% CI: 18.8, 34.0) and clinical benefit rate was 74.1% (95% CI: 66.0, 81.2). Overall, the adverse event (AE) profile was consistent with previous phase III trials. Neutropenia (68.3%), nausea (59.7%), and fatigue (54%) and neutropenia (48.9%) were the most common adverse events (all grades). Neutropenia was the most common AE leading to dose reduction (12.2%) or interruption (33.8%), with ALT increase the most common cause for treatment discontinuation (10.1%). QT prolongation (all grades) led to 3 (2.2%) dose interruptions and 2 (1.4%) dose reductions, but no treatment discontinuations. Conclusions: This subgroup analysis of the COMPLEEMENT-1 study provides further clinically meaningful outcomes on first-line ribociclib and letrozole treatment in a UK cohort. This treatment combination showed consistent efficacy and side effect profile in UK HR+, HER2- ABC patients, consistent with the overall ITT population as well as results observed in the other pivotal ribociclib registration studies. NCT02941926.

Citation Format: Mark Tuthill, Hardeep Marwaha, Christoph EA Hartmann. Phase 3b CompLEEment-1 study of ribociclib plus letrozole in the treatment of HR+/HER2- advanced breast cancer: Final results from the UK cohort [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS10-49.