4290 - Ribociclib (RIBO) + letrozole (LET) in patients (pts) with hormone receptor-positive (HR+), human epidermal growth factor receptor-2–negative (HER2–) advanced breast cancer (ABC) who received prior chemotherapy (CT) for advanced disease: Preliminary subgroup results from the phase 3b CompLEEment-1 trial

Background

CDK4/6 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). Previous first-line studies of CDK4/6 inhibitors plus an AI have excluded pts who have received prior CT for ABC, and as such it is important to define safety in this population. Here, we report early safety results for pts who had received prior CT for ABC enrolled in CompLEEment-1, an open-label, phase 3b trial evaluating RIBO+LET as first-line endocrine-based therapy in an expanded pt population.

Methods

Pts with HR+, HER2– ABC, ≤1 line of prior CT, and no prior endocrine therapy for ABC received RIBO (600 mg/day, 3 wk on/1 wk off) + LET (2.5 mg/day); men and premenopausal women received concomitant goserelin (3.6-mg subcutaneous implant q28 days). The primary outcome was safety and tolerability. A pre-planned interim analysis was conducted ∼15 months after first pt first visit.

Results

Of the first 1,008 pts enrolled with 56 days of follow-up or discontinued before the data cut-off, 188 had received prior CT for ABC. In this subgroup, the median age was 56.5 years; 2 pts were men and 39 were premenopausal women. The majority of pts (95%) had an Eastern Cooperative Oncology Group performance status ≤1; 45.7% presented with stage IV disease at diagnosis. The most common sites of metastasis were lung (38.8%), liver (33.0%), and lymph nodes (30.0%). The most common all-grade adverse events (AE) were neutropenia (48.9%), nausea (30.3%), and fatigue (20.7%). The most common grade ≥3 AEs were neutropenia (28.2%) and leukopenia (3.2%). QT prolongation events were mild and occurred in 5.9% of pts. Dose reduction or interruption due to AEs occurred in 48.4% of pts; 5 pts discontinued due to AEs.

Conclusions

Initial safety results from CompLEEment-1 demonstrate the tolerability of RIBO+LET in pts who had received prior CT for ABC, consistent with previous reports in pts without CT for ABC. NCT02941926.

Clinical trial identification

NCT02941926.

Legal entity responsible for the study

Novartis Pharmaceuticals.

Funding

Novartis Pharmaceuticals.

Editorial Acknowledgement

Financial support for medical editorial assistance was provided by Novartis Pharmaceuticals. We thank Holly C. Cappelli, PhD, ProEd Communications, Inc., for her medical editorial assistance with this abstract.

Disclosure

F. Cardoso: Consulting role: Astellas/Medivation, AstraZeneca, Celgene, Daichii-Sankyo, Eisai, GE Oncology, Genetech, GlaxoSmithKline, Macrogenics, Merck-Sharp, Merus BV, Mylan, Novartis, Pfizer, Amgen, Mundipharma, Pierre-Fabre, Roche, Sanofi, Seattle Genetics, Teva. K. Papazisis: Personal fees from Novartis, during the conduct of the study; Personal fees from Novartis, BMS; Personal fees and non-financial support from Roche, Amgen; Personal fees from AstraZeneca, outside the submitted work. M. De Laurentiis: Consulting or advisory role: AstraZeneca, Celgene, Lilly, Novartis, Pfizer, and Roche; Honoraria: AstraZeneca, Celgene, Novartis, Pfizer, and Roche. A. Ring: Consulting or advisory role: Pfizer and Roche; Honoraria: AstraZeneca, Lilly, Novartis, Pfizer, and Roche; Research funding; AstraZeneca. J. Lu: Travel, accommodations, expenses: Novartis. M. Martín: Consulting or advisory role: Amgen, Lilly, Novartis, Pfizer, PharmaMar, Roche/Genentech Research funding: Novartis. H.A. Azim: Employment: Innate, France (immediate family member); Consulting or advisory role: AstraZeneca, Bristol-Myers Squibb, Janssen, MSD, Novartis, Pfizer, and Roche; Honoraria: Amgen, AstraZeneca, Bristol-Myers Squibb, MSD, Novartis, Pfizer, and Roche; Research funding: Pfizer. C. Zamagni: Consulting or advisory role: AstraZeneca, Eisai, Novartis, Pfizer, PharmaMar, Pierre Fabre, and Roche; Travel, accommodations, expenses: Celgene, Novartis, Pierre Fabre; Roche Research funding: AbbVie, Array BioPharma, AstraZeneca, Celgene, Medivation, Morphotek, Novartis, Pfizer, Roche, and Roche/Genentech. K. Zhou, J.P. Zarate: Employee: Novartis. J. Wu: Employee of Novartis; Employment: Janssen (immediate family member); Travel, accommodations, expenses: Janssen (immediate family member). P.H. Cottu: Consulting or advisory role: Novartis and Pfizer; Travel, accommodations, expenses: Novartis, Pfizer, and Roche; Honoraria: AstraZeneca, NanoString Technologies, Novartis, Pfizer, and Roche; Research funding: AstraZeneca, Genentech/Roche, Novartis, Pierre Fabre, and Pfizer.