Ribociclib (RIBO) + letrozole (LET) in premenopausal patients (pts) with hormone receptor-positive (HR+), human epidermal growth factor receptor-2–negative (HER2–) advanced breast cancer (ABC) with no prior endocrine therapy (ET) for ABC: Preliminary subgroup results from the phase IIIb CompLEEment-1 trial
Authors: H. Abdel-Razeq, P.H. Cottu, A. Ring, M. De Laurentiis, J. Lu, H.A. Azim, C. Zamagni, K. Zhou, J. Wu, L. Menon, M. Martín
Journal: Annals of Oncology (2018)

Background: CDK4/6 inhibitor RIBO significantly improved progression-free survival in combination with ET versus placebo + ET in pre- and postmenopausal women with HR+, HER2– ABC and no prior therapy for advanced disease in the pivotal phase 3 MONALEESA-7 and MONALEESA-2 trials (Tripathy et al. SABCS 2018; Hortobagyi et al. NEJM 2016). Here, we report additional safety data for RIBO+LET in premenopausal female pts enrolled in CompLEEment-1, an open-label, phase 3b trial evaluating RIBO+LET as first-line therapy in an expanded pt population. Methods: Premenopausal pts with HR+, HER2– ABC, ≤1 line of prior chemotherapy, and no prior ET for ABC received RIBO (600 mg/day, 3 wk on/1 wk off) + LET (2.5 mg/day) and 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 pt first visit. Results: Of the first 1,008 pts enrolled who completed 56 days of follow-up or discontinued before data cut-off, 153 were premenopausal women. Median age was 45.0 years and the majority of pts (99.3%) had an Eastern Cooperative Oncology Group performance status ≤1; 40.5% had stage IV disease at diagnosis. Bone (73.9%), lung (31.4%), and liver (30.7%) were the most common metastatic sites. The most frequent adverse events (AEs) were neutropenia (53.6%), nausea (30.1%), hot flush (20.9%), headache (17.0%), and asthenia (16.3%). The most frequent grade ≥3 AE was neutropenia (34.0%). QT prolongation was infrequent (2.0%). Dose adjustment/treatment interruption due to AEs was required for 48.4% of pts. Four patients (2.6%) discontinued treatment due to AEs. Conclusions: Initial safety results from CompLEEment-1 demonstrate the tolerability of RIBO+LET + ovarian functional suppression in premenopausal women, consistent with previous reports. NCT02941926. Clinical trial identification: NCT02941926. Editorial acknowledgement: Financial support for medical editorial assistance was provided by Novartis Pharmaceuticals. We thank Elise Blankenship, PhD, ProEd Communications, Inc., for her medical editorial assistance with this abstract. Legal entity responsible for the study: Novartis Pharmaceuticals. Funding: Novartis Pharmaceuticals. Disclosure: P.H. Cottu: Consulting or advisory role: Novartis and Pfizer; Travel, accommodations, expenses: Novartis, Pfizer, Roche; Honoraria: AstraZeneca, NanoString Technologies, Novartis, Pfizer, Roche; Research funding: AstraZeneca, Genentech/Roche, Novartis, Pierre Fabre, and Pfizer. A. Ring: Consulting or advisory role: Pfizer and Roche; Honoraria: AstraZeneca, Lilly, Novartis, Pfizer, Roche; Research funding: AstraZeneca. M. De Laurentiis: Consulting or advisory role: AstraZeneca, Celgene, Lilly, Novartis, Pfizer, Roche Honoraria: AstraZeneca, Celgene, Novartis, Pfizer, and Roche. J. Lu: Personal fees: Novartis; Personal fees from outside the submitted work; Syndex. H.A. Azim: Employment: Innate, France (immediate family member); Consulting or advisory role: AstraZeneca, Bristol-Myers Squibb, Janssen, MSD, Novartis, Pfizer, Roche; Honoraria: Amgen, AstraZeneca, Bristol-Myers Squibb, MSD, Novartis, Pfizer, Roche; Research funding: Pfizer. C. Zamagni: Consulting or advisory role: AstraZeneca, Eisai, Novartis, Pfizer, PharmaMar, Pierre Fabre, Roche; Travel, accommodations, expenses: Celgene, Novartis, Pierre Fabre, Roche; Research funding: AbbVie, Array BioPharma, AstraZeneca, Celgene, Medivation, Morphotek, Novartis, Pfizer, Roche, Roche/Genentech. K. Zhou, L. Menon: Employee: Novartis. J. Wu: Employee of Novartis; Employment: Janssen (immediate family member); Travel, accommodations, expenses: Janssen (immediate family member). M. Martín: Consulting or advisory role: Amgen, Lilly, Novartis, Pfizer, PharmaMar, Roche/Genentech; Research funding: Novartis. All other authors have declared no conflicts of interest.