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CompLEEment-1 (NCT02941926) is a single-arm, open-label, multicentre phase IIIb study investigating the safety and efficacy of ribociclib plus letrozole (RIB + LET) in a large, diverse cohort who have not received prior endocrine therapy (ET) for advanced disease. We present an exploratory analysis of male patients.Eligible patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC), who had no prior ET and ≤ 1 line of prior chemotherapy for advanced disease, received RIB + LET. Male patients also received goserelin or leuprolide. Primary endpoint was safety and tolerability; efficacy was a secondary endpoint.In total, 39/3246 patients were male. Baseline characteristics were similar to the overall population. Male patients experienced fewer treatment-related adverse events (AEs) and treatment-related serious AEs compared with the overall population; fewer male patients had treatment-related AEs leading to discontinuation, adjustment/interruption, or additional therapy. One male patient died as a result of a serious AE that was not considered to be treatment-related. The most common AE was neutropenia; the incidence of grade ≥ 3 neutropenia in males (41.0%) was lower than in the overall population (57.2%). Median follow-up was 25.4 months; median time to progression was not reached in males versus 27.1 months for the overall population.The clinical benefit and overall response rates in males were consistent with the overall population. This analysis demonstrates the safety and efficacy of ribociclib in a close-to-real-world setting, supporting the use of RIB + LET in male patients with HR+, HER2- ABC.NCT02941926 (Registered 2016).

Background: While the incidence of breast cancer in men is up to 100-fold less than in women, it is estimated that in 2020, 2,620 men in the United States will be diagnosed with breast cancer, and 520 will die from this disease. However, male patients are rarely included in breast cancer clinical trials and treatment guidelines for this population are often proposed based on data from female patients. Ribociclib (RIB), an oral, selective cyclin-dependent kinase 4/6 inhibitor, is approved for use in combination with endocrine therapy (ET) in women with HR+, HER2- ABC. Here, we present a subgroup analysis of male patients from the Core Phase of CompLEEment-1 (NCT02941926), a Phase IIIb trial of RIB in combination with letrozole (LET) in patients with HR+, HER2- ABC. In order to reflect a more typical real-world clinical setting, the eligibility criteria for this study allowed for a more diverse and broader patient population than those of previous Phase III trials of RIB + LET. Methods: CompLEEment-1 included women of any menopausal status and men with HR+, HER2- ABC treated with ≤1 line of prior chemotherapy and no prior hormonal therapy for advanced disease. Pts received RIB (600 mg QD, 3 weeks on/1 week off) in combination with LET (2.5 mg QD, continuous). Men and premenopausal women received a luteinizing hormone-releasing hormone agonist (3.6 mg goserelin or 7.5 mg leuprolide, Q28D). This subgroup analysis assessed the primary outcomes (safety and tolerability) and secondary outcomes of time to progression (TTP), overall response rate (ORR), and clinical benefit rate (CBR) in male patients. Results: At the data cutoff date (November 8, 2019), 39 male patients (1.2%; N = 3,246) had been evaluated, with a median duration of exposure to RIB of 19.2 months. Adverse events (AEs) were reported in 38 (97.4%) patients; with all but two experiencing a treatment-related AE. Grade ≥ 3 AEs were reported in 26 (66.7%) patients; serious AEs were reported in 6 patients. There were no treatment-related fatal AEs. The most common all-grade AEs were neutropenia (53.8%), hot flush (33.3%), and diarrhea (25.6%), with the most common grade ≥ 3 AE being neutropenia (41.0%). Overall, 7 patients (17.9%) had ≥ 1 dose reduction of RIB, all of whom had at least 1 due to an AE, and 18 patients (46.2%) permanently discontinued treatment, 4 (10.3%) due to AEs. Median TTP was not estimable (95% CI, 16.8-NE); event-free probability was 61.4% (95% CI, 38.4-77.9) at 30 months. For the 32 patients with measurable disease, ORR was 46.9% (95% CI, 29.1-65.3%) and CBR was 71.9% (95% CI, 53.3-86.3). Conclusions: In this subgroup analysis of male patients - a rare population who are often excluded from clinical trials - efficacy results support the use of RIB + LET in HR+, HER2- ABC in a close to real-world setting. The safety profile associated with RIB + LET was manageable, with very few patients discontinuing treatment due to AEs, consistent with previous Phase III trials of RIB + LET. Citation Format: Mario Campone, Michelino De Laurentiis, Claudio Zamagni, Igor Kudryavcev, Mariëtte Agterof, Ursa Brown-Glaberman, Markéta Pálácova, Sanjoy Chatterjee, Lakshmi Menon-Singh, Jiwen Wu, Katie Zhou, Miguel Martín. Ribociclib + letrozole in male patients with hormone receptor-positive (HR+), human epidermal growth factor receptor-2-negative (HER2−) advanced breast cancer (ABC): Subgroup analysis of the phase IIIb CompLEEment-1 trial [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 PS14-03.