Abstract PS10-10: Ribociclib + letrozole in premenopausal 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
Authors: Razeq Hikmat Abdel , Cottu Paul , Ring Alistair , De Laurentiis Michelino , Lu Janice , Azim Hamdy , Zamagni Claudio , Zhou Katie , Wu Jiwen , Menon-Singh Lakshmi , Martín Miguel 
Published: February 2021

Abstract
Background: The oral, selective cyclin-dependent kinase 4/6 inhibitor, ribociclib (RIB), has demonstrated significant overall survival benefit in combination with endocrine therapy (ET) in premenopausal patients with HR+, HER2- ABC. Here, we present a subgroup analysis of premenopausal 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, which included a more diverse and broader patient population, reflecting a real-world clinical setting. 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 premenopausal women. Baseline and end-of-treatment patient quality of life (QoL) was also measured in patients from selected countries as a secondary endpoint using the FACT-B questionnaire. Results: At the data cutoff date (November 8, 2019), 722 premenopausal patients (22.2%; N = 3,246) had been evaluated, with a median duration of exposure to RIB of 18.3 months. Adverse events (AEs) were reported in 710 (98.3%) patients; 681 (94.3%) patients had treatment-related AEs. Grade ≥ 3 AEs were reported in 519 (71.9%) patients; severe treatment-related AEs were reported in 26 (3.6%) patients. There were no treatment-related fatal AEs. The most common all-grade AEs were neutropenia (76.9%), nausea (36.0%), and leukopenia (27.6%). The most common grade 3/4 AEs were neutropenia (57.9%), leukopenia (10.4%), and increased alanine aminotransferase (5.7%). Overall, 242 (33.5%) patients had ≥ 1 dose reduction of RIB, 170 (23.5%) due to AEs. 413 (57.2%) patients permanently discontinued treatment, 67 (9.3%) due to AEs. In this subgroup analysis, median TTP was 25.1 months (95% confidence interval [CI], 22.1-not estimable). For the 458 patients with measurable disease, ORR was 49.3% (95% CI, 44.7-54.0%) and CBR was 69.7% (95% CI, 65.2-73.8). FACT-B questionnaire assessments showed a trend that patient QoL was maintained while on treatment (n = 290). Conclusions: This subgroup analysis from CompLEEment-1 supports the use of RIB + LET in premenopausal patients. ORR was similar to that seen in the Phase III MONALEESA-7 trial which studied RIB + ET in a premenopausal patient population, validating the efficacy of RIB in a close-to-real-world setting. The safety profile associated with RIB + LET was manageable and consistent with previous Phase III trials of RIB + LET.
Citation Format: Hikmat Abdel Razeq, Paul Cottu, Alistair Ring, Michelino De Laurentiis, Janice Lu, Hamdy Azim, Claudio Zamagni, Katie Zhou, Jiwen Wu, Lakshmi Menon-Singh, Miguel Martín. Ribociclib + letrozole in premenopausal 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 PS10-10.