Abstract P6-18-16: Ribociclib (RIBO) + letrozole (LET) in older patients with hormone receptor-positive (HR+), human epidermal growth factor receptor-2–negative (HER2–) advanced breast cancer (ABC): Preliminary subgroup results from the phase 3b CompLEEment-1 trial
Authors: Ring A , Borstnar S , Ferreira A , Azim HA , Cottu P , Lu J , Martin M , Zamagni C , Beck JT , Zhou K , Wu J , Menon L , De Laurentiis M 
Published: May 2019

Abstract
Background: The cyclin-dependent kinase (CDK)4/6 inhibitor RIBO is approved in combination with an aromatase inhibitor (AI) for HR+, HER2– ABC in postmenopausal women with no prior therapy for ABC, based on the MONALEESA-2 trial (Hortobagyi et al. NEJM 2016). Although a high proportion of patients with HR+, HER2– ABC are &gt;65 years of age, older patients are often under-represented in clinical trials. Furthermore, treatment decisions may be complicated by comorbidities, functional status, and concurrent medications. Here, we report early safety results for patients ≥65 years of age enrolled in CompLEEment-1, an open-label, phase 3b trial evaluating RIBO+LET as first-line endocrine-based therapy in an expanded patient population.
Methods: Patients with HR+, HER2– ABC, ≤1 line of prior chemotherapy (CT), and no prior endocrine therapy for ABC received RIBO (600 mg/day, 3 weeks on/1 week off) + LET (2.5 mg/day); men and premenopausal women received concomitant goserelin (3.6-mg subcutaneous implant every 28 days). The primary outcome was safety and tolerability. A pre-planned interim analysis was conducted ˜15 months after first patient first visit.
Results: Of the first 1,008 patients enrolled who completed 56 days of follow-up or discontinued before the data cut-off date, 377 were ≥65 years of age. Of these, 157 (41.6%) were 65-&lt;70 years, 107 (28.4%) were 70-&lt;75 years, and 113 (30%) were ≥75 years. The majority of patients (94.4%) had an Eastern Cooperative Oncology Group performance status ≤1; 33.2% presented with stage IV disease at diagnosis; 9 patients were male. The most common sites of metastasis were bone (70.0%), lung (44.8%), and lymph nodes (29.7%). The most common all-grade adverse events (AEs) were neutropenia (58.4%), nausea (31.8%), and fatigue (24.1%). The most common grade 3/4 AEs were neutropenia (37.7%) and alanine aminotransferase increase (4.2%). QT prolongation events were mild (majority grade 1/2) and occurred in 6.1% of patients (0.5% grade 3/4). Dose reduction or interruption due to AEs occurred in 54.5% of patients; 6.9% of patients had AEs leading to treatment discontinuation. In the overall patient population, the most frequent grade 3/4 AEs were neutropenia (42.8%), leukopenia (3.4%), and increased alanine aminotransferase (2.9%); QT prolongation occurred in 5.4% of patients (0.5% grade 3/4).
Conclusions: Initial safety results from CompLEEment-1, from the first 56 days of follow-up, demonstrate the tolerability of RIBO+LET in older patients, consistent with the overall patient population. NCT02941926.
Citation Format: Ring A, Borstnar S, Ferreira A, Azim HA, Cottu P, Lu J, Martin M, Zamagni C, Beck JT, Zhou K, Wu J, Menon L, De Laurentiis M. Ribociclib (RIBO) + letrozole (LET) in older patients with hormone receptor-positive (HR+), human epidermal growth factor receptor-2–negative (HER2–) advanced breast cancer (ABC): Preliminary subgroup results from the phase 3b CompLEEment-1 trial [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-18-16.