4024 - Ribociclib (RIB) + letrozole (LET) in patients (pts) with hormone receptor-positive (HR+), human epidermal growth factor receptor-2–negative (HER2–) advanced breast cancer (ABC) and central nervous system (CNS) metastases: Subgroup analysis from the phase 3b CompLEEment-1 trial

Background

CNS metastases are a risk in pts with breast cancer, with brain metastases diagnosed in 10-20% of pts. RIB, an oral, selective CDK4/6 inhibitor, is approved for use in combination with endocrine therapy (ET) in women with HR+, HER2– ABC in multiple countries. Here, we present a subgroup analysis of pts with CNS metastases from CompLEEment-1 (NCT02941926), an open-label, phase 3b trial evaluating RIB + LET as first-line therapy in an expanded population.

Methods

Pts (N = 3,246) with HR+, HER2– ABC and no prior ET for ABC received RIB (600 mg/day, 3 weeks on/1 week off) + LET (2.5 mg/day); concomitant goserelin (3.6 mg every 28 days) or leuprolide (7.5 mg every 28 days) was used in men and premenopausal women. In this subgroup analysis of 50 pts with CNS metastases, we assessed the primary outcomes (safety and tolerability) and time to progression (TTP), overall response rate (ORR), and clinical benefit rate (CBR).

Results

In pts with CNS metastases, the median duration of follow-up was 10.35 months and median duration of exposure to RIB was 7.8 months. Adverse events (AEs) were reported in 48 (96%) pts; 46 pts had treatment-related AEs. Grade 3/4 AEs were reported in 34 (68%) pts; 4 severe AEs were reported. There was 1 treatment-related fatal AE (sepsis). The most common all-grade AEs were neutropenia (52%), nausea (36%), and fatigue (26%). The most common grade 3/4 AEs were neutropenia (40%), neutrophil count decreased (14%), leukopenia (6%), and increased AST (6%) and ALT (6%). No neurological AEs were recorded. Seventeen (34%) pts had ≥ 1 dose reduction of RIB, 12 due to AEs, and 18 (36%) pts permanently discontinued treatment, 5 due to AEs. Median TTP was 16 months (95% CI, 16.0-NE) in pts with CNS metastasis; treatment of 32 (64%) pts was ongoing by cut-off date. For pts with measurable disease, ORR was 41.2% (95% CI, 24.6-59.3%) and CBR was 61.8% (95% CI, 43.6-77.8%).

Conclusions

This subgroup analysis from CompLEEment-1 supports the safety and efficacy of RIB + LET in pts with CNS metastasis. Additional patient follow-up is ongoing.

Clinical trial identification

NCT02941926.

Editorial acknowledgement

Medical editorial assistance was provided by Heyuan Sun, PhD, of Healthcare Consultancy Group, LLC, and funded by Novartis Pharmaceuticals Corporation.

Legal entity responsible for the study

Novartis.

Funding

Novartis Pharmaceuticals.

Disclosure

M. De Laurentiis: Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Celgene; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Eisai; Honoraria (self), Advisory / Consultancy: Eli Lilly; Honoraria (self), Advisory / Consultancy: Amgen. P. Marchetti: Advisory / Consultancy: Novartis; Advisory / Consultancy: BMS; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Incyte; Advisory / Consultancy: Molteni; Advisory / Consultancy: Roche; Advisory / Consultancy: MSD. F.P. Duhoux: Research grant / Funding (institution): Novartis; Honoraria (institution): Roche; Honoraria (institution): Pfizer; Honoraria (institution): AstraZeneca. All other authors have declared no conflicts of interest.