Abstract P5-11-17: Phase IIIb CompLEEment-1 study of ribociclib plus letrozole in the treatment of HR+/HER2- advanced breast cancer (ABC): Interim results from the UK cohort
Authors: Ring Alistair , Crook Timothy , Tuthill Mark , Roylance Rebecca , McGoldrick Trevor , Chan Stephen , Lo'Monte Helen , Roberts William 
Published: March 2020

Abstract
Background: Ribociclib, an oral, selective inhibitor of CDK4/6 (CDK4/6i), is approved for use in combination with endocrine therapy (ET) in women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) ABC in multiple countries, including the UK, based on three phase III registration studies (MONALEESA-2, -3 and -7). Ribociclib plus ET demonstrated significantly improved PFS in all the phase III studies compared with placebo plus ET and significantly increased OS in the 1st line study of premenopausal women (MONALEESA-7). Here we report interim safety and efficacy results from the UK cohort of CompLEEment-1, a phase 3b trial evaluating RIBO+LET in an expanded patient (pt) population. Methods: Pts with HR+, HER2- ABC, ≤1 line of prior chemotherapy (CT), and no prior ET for ABC received RIBO+LET. Treatment regimens and study endpoints have been reported previously (De Laurentiis, et al. ASCO 2018. Poster 1056). Results: Out of the 3,246 patients recruited globally, 139 patients who received ≥1 dose of study treatment at UK sites, were evaluated. At the cut-off date (August 8, 2018), 83 patients (59.3%) were still receiving treatment, with adverse events (20.9%) and progressive disease (12.9%) the most common reasons for discontinuation. Demographic and baseline characteristics indicated a diverse population including premenopausal women (9.4%), patients aged ≥70 years (25.2%) and ECOG ≥1 (35.9%; 1[34.5%], 2 [1.4%]). The median age of the participants was 62 yrs (range 34-86). De novo ABC was the most recent diagnosis in 18.7% of patients, 10.1% had DFI ≤24 months and 70.5% had DFI &gt;24 months. Visceral disease was present in 59.7% of patients, 24.5% had bone-only metastases, 2.9% had CNS metastases and the proportion of patients with ≥3 metastatic sites was 41.8%. The most common adverse events (all grades) were neutropenia (66.2%), nausea (59.0%) and fatigue (51.1%). AEs of special interest (AESI) and their clinical impact are shown in table 1. The only non-hematologic any-cause grade ≥3 AEs ≥5% were increased ALT (11.5%) and AST (7.2%). There were no on study deaths in the UK cohort. The overall response rate was 22.3% (95% CI: 15.7%, 30.1%) and clinical benefit rate was 71.2% (95% CI: 62.9%, 78.6%). Conclusions: This interim analysis provides safety, tolerability, and efficacy of ribociclib in combination with letrozole in UK pts with HR+, HER2- ABC who had not previously received ET for ABC. Safety results and response rates were consistent with those observed in the international phase III registration studies. NCT02941926.
Table 1. Clinical impact of AESI, n (%)NeutropeniaALT increasedAST increasedQTcF prolongationAll grade92 (66.2)29 (20.9)24 (17.3)10 (7.2)Grade 3/469 (49.6)16 (11.5)10 (7.2)1 (0.7)Leading to dose interruption63 (45.3)13 (9.4)14 (10.1)3 (2.2)Leading to dose reduction21 (15.1)1 (0.7)0 (0)2 (1.4)Leading to dose withdrawal0 (0)13 (19.4)6 (4.3)0 (0)Leading to hospitalization4 (2.9)0 (0)0 (0)0 (0)
Citation Format: Alistair Ring, Timothy Crook, Mark Tuthill, Rebecca Roylance, Trevor McGoldrick, Stephen Chan, Helen Lo'Monte, William Roberts. Phase IIIb CompLEEment-1 study of ribociclib plus letrozole in the treatment of HR+/HER2- advanced breast cancer (ABC): Interim results from the UK cohort [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-11-17.