Analysis of Ribociclib plus Letrozole in Male Patients with HR-Positive, HER2-Negative Advanced Breast Cancer

In 2020, it is estimated that 2620 men in the United States will be diagnosed with breast cancer, and 520 will die from the disease. Rarely are male patients included in breast cancer clinical trials, and treatment guidelines are often proposed based on data from female patients. This may be due in part to the incidence of breast cancer in men is 100-fold less than in women.

The oral, selective cyclin-dependent kinase 4/6 inhibitor, ribociclib (Kisqali), is approved for use in combination with endocrine therapy in women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer.

Mario Campone, MD, PhD, General Director, Institut de Cancérologie de l’Ouest, Nantes, France, and colleagues presented a subgroup analysis of male patients from the core phase of CompLEEment-1, a phase 3b trial of ribociclib administered in combination with letrozole in patients with HR-positive, HER2-negative advanced breast cancer. The eligibility criteria for this study allowed for a more diverse and broader patient population than those of previous phase 3 trials of ribociclib combined with letrozole, thereby reflecting a real-world clinical setting.

Including women of any menopausal status and men, CompLEEment-1 investigated the treatment of patients with HR-positive, HER2-negative advanced breast cancer treated with ≤1 lines of previous chemotherapy and no previous hormonal therapy for advanced disease. In this study, patients received ribociclib 600 mg daily for 3 weeks on then 1 week off, in combination with 2.5 mg letrozole continuously daily. Men and premenopausal women received a luteinizing hormone-releasing hormone agonist, either 3.6 mg goserelin or 7.5 mg leuprolide, every 28 days. Safety and tolerability were the primary outcomes of this subgroup analysis. The secondary outcomes were time to progression, overall response rate, and clinical benefit rate of male patients.

In this analysis, 39 (1.2% of 3246) male patients were evaluated with a median duration of ribociclib exposure of 19.2 months.

Two-thirds of patients experienced grade ≥3 adverse events, and serious adverse events were reported by 6 patients. No fatal treatment-related adverse events were reported.

The most common all-grade adverse events were neutropenia reported by 53.8% of men in the study, followed by hot flush experienced by 33.3% and diarrhea by 25.6%. The most common grade ≥3 adverse event reported was neutropenia that occurred in 41.0% of patients.

Nearly 18% of patients overall had ≥1 dose reductions of ribociclib, all of whom had at least 1 due to an adverse event, and 46.2% patients permanently discontinued treatment of which 10.3% was related to side effects.

Median time to progression was not possible to estimate; however, the event-free probability was 61.4% at 30 months. The overall response rate was 46.9% and the clinical benefit rate was 71.9% for the 32 patients with measurable disease.

Based on demonstrated efficacy and safety results of this subgroup analysis of male patients who have historically been excluded from clinical trials, the combination of ribociclib and letrozole in HR-positive, HER2-negative advanced breast cancer is supported.