Expanded Safety Analysis of the Phase 3b CompLEEment-1 Trial with Ribociclib plus Letrozole in Patients with Hormone Receptor–Positive, HER2-Negative Advanced Breast Cancer

In this broad study of a diverse population, adverse events associated with the combination of ribociclib plus letrozole were manageable and consistent with previous phase 3 trials of the same combination, and adverse events of special interest markedly decreased over time.

An ongoing phase 3b trial called the CompLEEment-1 study focuses on the use of ribociclib in combination with letrozole in the first-line setting for patients with hormone receptor–positive, HER2-negative advanced breast cancer. Differing from the pivotal MONALEESA trials, CompLEEment-1 includes a diverse patient population with the intention of providing real-world data.

Janice Lu, MD, Clinical Professor, Medical Oncology, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, and colleagues reported from the completed core phase of the trial and further analyses of the primary end point of safety. Included in this study were men and women of any menopausal status with hormone receptor–positive, HER2-negative advanced breast cancer who were treated with ≤1 lines of previous chemotherapy and no previous hormonal therapy for advanced disease.

Patients who were prescribed ribociclib 600 mg daily for 3 weeks on and 1 week off in combination with continuous letrozole 2.5 mg daily were included in the study. Men and premenopausal women were prescribed a luteinizing hormone-releasing hormone agonist (3.6 mg goserelin or 7.5 mg leuprolide every 28 days). Safety and tolerability were the primary end points. Updated assessments included clinical impact of adverse events of special interest, dose reduction/interruption or treatment discontinuation due to adverse events, and exposure-adjusted incidence/occurrence rates for adverse events of special interest.

By November 8, 2019, at data cutoff, 3246 patients had been evaluated. Median duration of exposure to ribociclib was 17.5 months with a median follow-up of 25.4 months. A total of 1301 (40.1%) patients completed the core phase treatment, and 415 patients proceeded to the extension phase.

Overall, patient discontinuation of treatment was high, with 1945 (59.9%) patients permanently discontinuing treatment due primarily to adverse events (15.5%) and progressive disease (34.2%). The vast majority (N = 3091; 95.2%) of patients reported treatment-related adverse events, leading to dose modification in more than two-thirds of the patients (N = 2235; 68.9%).

In patients who had grade ≥3 neutropenia, dose modification occurred most often (dose interruption, N = 1671 [51.5%]; dose reduction, N = 480 [14.8%]); treatment discontinuation occurred most frequently in patients with grade ≥3 increased alanine aminotransferase (ALT; N = 116 [3.6%]) or aspartate aminotransferase (AST; N = 68 [2.1%]). Grade ≥3 neutropenia appeared in 1856 (57.2%) patients, with the median duration of first occurrence of 1.1 weeks and median time to first occurrence of 4.1 weeks. Laboratory findings demonstrated grade ≥2 increased ALT and AST occurring in 453 (14.0%) and 380 (11.7%) patients, respectively. Infrequently, grade ≥2 Fridericia’s QT corrected prolongation occurred in 101 (3.1%) patients, leading 8 (0.2%) patients to treatment discontinuation. Adverse events of special interest infrequently led to hospitalization (0%-0.3%) and there were no fatal incidents. Showing a marked decrease, the incidence/occurrence rates and the adverse event rates of special interest declined by a factor of ×2 to ×8 from 0 to 1 year when compared with 1 to 2 years, as exposure-adjusted incidence rates for adverse events of special interest per 100 patient-years of exposure demonstrated that with increasing ribociclib exposure.

With the combination of ribociclib plus letrozole, associated adverse events were manageable and consistent with previous phase 3 trials. From year 1 to year 2 of treatment, the adjusted incidence/occurrence rates for adverse events of special interest markedly decreased. In men and women of any menopausal status and in a broader and more diverse patient population, this study further supports the use of ribociclib plus letrozole for first-line treatment of hormone receptor–positive, HER2-negative advanced breast cancer.

Source: Lu J, Cottu P, Martin M, et al. Ribociclib + letrozole in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor-2-negative (HER2−) advanced breast cancer (ABC): expanded safety analysis of the phase IIIb CompLEEment-1 trial. Presented at: 2020 San Antonio Breast Cancer Symposium, December 8-11, 2020. Abstract PS10-05.