In the MONALEESA-7 study (NCT02278120), RIB + TAM/NSAI + goserelin significantly prolonged progression-free survival (PFS) and had a manageable safety profile vs placebo (PBO) + TAM/NSAI in premenopausal pts with HR+, HER2– ABC. Here we present data for the TAM and NSAI subgroups.
Premenopausal pts (N = 672) with HR+, HER2– ABC (≤1 line of chemotherapy; no prior endocrine therapy [ET] for ABC) were randomized 1:1 to RIB (600 mg/day, 3 weeks on/1 week off) or PBO + either TAM (20 mg/day) or NSAI (letrozole [2.5 mg/day] or anastrozole [1 mg/day]) + goserelin (3.6 mg every 28 days). Primary endpoint: locally assessed PFS. A predefined subgroup analysis evaluated PFS by ET partner (TAM or NSAI).
177 (26%) pts received TAM (RIB vs PBO: 87 vs 90) and 495 (74%) received an NSAI (248 vs 247). As of August 20, 2017, treatment was ongoing in 49% vs 31% of pts in the TAM subgroup and 53% vs 38% in the NSAI subgroup; the most common reason for discontinuation was disease progression (TAM 39% vs 54%; NSAI 35% vs 51%). PFS was prolonged for RIB vs PBO in the TAM (median 22.1 months [mo] vs 11.0 mo; hazard ratio 0.585; 95% CI 0.387–0.884) and NSAI (median 27.5 mo vs 13.8 mo; hazard ratio 0.569; 95% CI 0.436–0.743) subgroups. The most common Grade (G) 3 adverse events (AEs; regardless of causality; ≥5% of pts; RIB vs PBO) were neutropenia (TAM 39% vs 2%; NSAI 55% vs 3%), leukopenia (TAM 8% vs 1%; NSAI 15% vs 1%), elevated GGT (TAM 6% vs 3%; NSAI <1% vs 4%), elevated ALT (TAM 7% vs 2%; NSAI 5% vs 1%), and hypertension (TAM 6% vs 2%; NSAI 2% vs 3%); the only G4 AE in ≥ 5% of pts was neutropenia (TAM 9% vs 1%; NSAI 10% vs < 1%). Increases >60 ms from baseline in the QTcF interval (RIB vs PBO; TAM 16% vs 7%; NSAI 7% vs 0%) and new QTcF >480 ms (TAM 11% vs 1%; NSAI 5% vs 1%) were more common with TAM; there were no associated clinical symptoms or arrhythmias.
RIB demonstrated consistent treatment benefit vs PBO in premenopausal pts with HR+, HER2– ABC regardless of ET partner (TAM or NSAI). The safety profiles of RIB + ET were manageable and consistent, with the exception of QTc findings, which were more prevalent with TAM.
Clinical trial identification
NCT02278120 and October 29, 2014.
Legal entity responsible for the study
Novartis Pharmaceuticals Corporation.
Novartis Pharmaceuticals Corporation.
Editorial assistance was provided by Kate Gaffey PhD of ArticulateScience Ltd.
A. Bardia: Advisory role: Novartis, Genentech, Pfizer, Spectrum Pharma and Biothernostics. S. Campos-Gomez: Consulting/advisory role: Roche, outside submitted work. S.A. Hurvitz: Grants: Amgen, Bayer, BI Pharma, Genentech, GSK, Lilly, Novartis, Pfizer, Roche, PUMA, Merrimack, Medivation, Dignatana, OBI Pharma, Biomarin, Cascadian, Seattle Genetics; Travel expenses: Lilly, Novartis, OBI Pharma, Bayer outside the submitted work. Grants: Novartis, grants and non-financial support: Roche, grants and non-financial support: Merck, grants: AstraZeneca, outside the submitted work; Honoraria, speaker/consulting role, speakers bureau: Roche, Novartis, AstraZeneca, Pfizer. S-A. Im: Personal fees: Novartis; Advisory role: Pfizer, during the conduct of the study; Advisory role: Hanmi, Roche; Research grants: AstraZeneca, outside the submitted work. L. Chow: Travel, accommodation and expenses fees: Roche, Novartis, Pfizer. P. Wheatley-Price: Personal fees: Novartis, AstraZeneca, Lilly Oncology, BMS, Merck, Takeda, during the conduct of the study. J. Alam: Employment: Novartis Pharmaceutical Corporation. O. Kong, I. Diaz-Padilla, M. Miller: Employment and equity ownership: Novartis Pharmaceutical Corporation. D. Tripathy: Grants, personal fees and support for abstract/manuscript and support for conducting trial (paid to institution), consulting fees for service on the trial Steering Committee from Novartis, during the conduct of the study; Consulting fees: Pfizer, outside the submitted work. All other authors have declared no conflicts of interest.