Ribociclib (Kisqali) is an oral, selective cyclin-dependent kinase 4/6 inhibitor that has demonstrated significant overall survival benefit when prescribed in combination with endocrine therapy in premenopausal patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer.
Hikmat Abdel Razeq, MD, Chief Medical Officer and Deputy Director General, King Hussein Cancer Center, Amman, Jordan, presented a subgroup analysis of premenopausal patients in the phase 3b CompLEEment-1 clinical trial. Women of any menopausal status as well as men with HR-positive, HER2-negative advanced breast cancer who were treated with ≤1 lines of previous chemotherapy and no previous hormonal therapy for advanced disease were included in the CompLEEment-1 study. Participants received in combination with continuous letrozole (Femara) treatment (2.5 mg once daily), ribociclib at a dose of 600 mg once daily for 3 weeks on, then 1 week off. Every 28 days, participants received a luteinizing hormone-releasing hormone agonist, either 3.6 mg goserelin or 7.5 mg leuprolide.
Safety and tolerability were the primary outcomes, and the secondary outcomes were time to progression, overall response rate (ORR), and clinical benefit rate in premenopausal women. Patient-reported quality of life was also measured as a secondary end point at baseline and at end of treatment.
In this subgroup analysis, reflecting a real-world clinical setting, which included a more diverse and broader patient population, ribociclib was given in combination with letrozole in premenopausal women with HR-positive, HER2-negative advanced breast cancer.
A total of 722 premenopausal patients (22.2% of a total of the 3246 participants) were evaluated, with a median duration of treatment with ribociclib of 18.3 months. Side effects were reported in 98.3% of patients, with 94.3% of patients reporting treatment-related side effects. In 71.9% of patients, grade ≥3 side effects were reported. Severe treatment-related side effects were reported in 3.6% of patients and no treatment-related deaths.
The most common all-grade adverse effects were neutropenia reported in more than three-quarters (76.9%) of patients, followed by nausea (36.0%) and leukopenia (27.6%). The most common grade 3/4 adverse effects were neutropenia reported in 57.9% of patients, followed by 10.4% of patients having leukopenia and an increased alanine aminotransferase level in 5.7% of patients. Overall, 33.5% of patients had ≥1 dose reductions of ribociclib, 23.5% due to side effects. More than half (57.2%) of patients permanently discontinued treatment, with 9.3% of discontinuations due to side effects.
Median time to progression was 25.1 months in this subgroup analysis. For the 458 patients with measurable disease, the ORR was 49.3% and the clinical benefit rate was 69.7%. The quality of life of some patients (N = 290) was reportedly maintained while receiving treatment.
This subgroup analysis from CompLEEment-1 confirms the positive impact of ribociclib plus letrozole treatment in premenopausal women. In this study, the objective response rate was similar to that seen in the MONALEESA-7 trial, which investigated ribociclib combined with endocrine therapy in a premenopausal patient population, supporting the efficacy of ribociclib based on data that are closer to real-world settings. The manageable and consistent safety profile aligned with previous phase 3 trials.