Updated Results from the Phase 3b CompLEEment-1 Study of Ribociclib plus Letrozole in the Treatment of Hormone Receptor–Positive, HER2-Negative Advanced Breast Cancer

In a large, diverse cohort of patients, this analysis confirms the safety and efficacy of ribociclib plus letrozole with data that are consistent with those observed in the MONALEESA trials, supporting the use of this combination in the first-line setting.

The critical importance of real-world evidence is highlighted in this study, as it complements data from randomized controlled trials. Expanding on previous findings, Michelino De Laurentiis, MD, PhD, Head, Breast Oncology, Istituto Nazionale Tumori, National Institute for Research and Treatment, Naples, Italy, and colleagues reported updated results from CompLEEment-1, a phase 3b clinical trial evaluating ribociclib plus letrozole in the largest CDK4/6 inhibitor trial in patients with advanced breast cancer. To date, this is the largest trial of CDK4/6 inhibitors in the advanced breast cancer population.

Included in this study were patients who received ribociclib plus letrozole, have hormone receptor–positive, HER2-negative advanced breast cancer, and who received ≤1 lines of previous chemotherapy and no previous endocrine therapy. Safety and tolerability were the primary end points in this study of 3246 patients who received ≥1 doses of study treatment. Median duration of follow-up was 25.4 months with 15 additional months since interim analysis.

The population reflected in this study was diverse. The median exposure to treatment was 17.8 months and included 1.2% men and 22.2% premenopausal women. Approximately 20% of the study population were aged >70 years (19.5%), and 3.5% of patients had an Eastern Cooperative Oncology Group performance status of 2. Six percent of patients had been treated previously with chemotherapy for advanced breast cancer, and 1.6% of patients had stable central nervous system lesions. Nearly two-thirds of patients experienced neutropenia (61.1%), 35.9% experienced nausea, and 23.4% experienced fatigue; these were the most commonly reported adverse events. Grade 3/4 hematologic abnormalities included decreased neutrophils, which were experienced by more than half of the study population (54.8%), as well as lymphocytes (12.6%) and leukocytes (25.9%). Grade 3/4 biochemical abnormalities included increased alanine aminotransferase (9.1%) and aspartate aminotransferase (6.7%).

Contributing to treatment discontinuation were treatment-related adverse events reported by 418 (12.9%) patients. A small percentage of deaths were due to breast cancer (1.2%). Median time to progression was 27.1 months (95% confidence interval [CI], 25.7-not established), overall response rate was 43.6% (95% CI, 41.5%-45.8%), and clinical benefit rate was 69.1% (95% CI, 67.1%-71.1%) for patients with measurable disease at baseline.

Closely resembling real-world clinical practice, this study, conducted in a large, diverse cohort, strongly suggests the safety and efficacy of ribociclib plus letrozole when treating patients with hormone receptor–positive, HER2-negative disease with no previous exposure to endocrine therapy for advanced breast cancer. The data are consistent with previous MONALEESA trials, suggesting a consistent safety and efficacy profile, and supporting the use of this combination as first-line therapy.

Source: De Laurentiis M, Borstnar S, Campone M, et al. Updated results from the phase IIIb complement-1 study of ribociclib (RIB) plus letrozole (LET) in the treatment of HR+, HER2-advanced breast cancer (ABC). J Clin Oncol. 2020;38(15_suppl). Abstract 1055.