RIB + FUL prolonged PFS vs placebo (PBO) + FUL in postmenopausal patients (pts) with HR+, HER2– ABC in the Phase 3 MONALEESA-3 study (NCT02422615). Consistent PFS benefit was observed in pts receiving treatment in either the first- (1L) or combined second-line (2L)/early relapse settings. Here we present additional efficacy and pain reduction results from MONALEESA-3.
Pts who received no or ≤ 1 line of prior endocrine therapy for ABC (i.e. receiving treatment in the 1L or 2L/early relapse settings, respectively) received RIB + FUL (n = 484) or PBO + FUL (n = 242). Endpoints included, primary: local PFS; secondary: overall response rate and health-related quality of life (HRQoL).
As of Nov 3, 2017, median PFS was prolonged for RIB vs PBO in the separate 2L and early relapse settings (Table). Amongst the full population, 155/379 pts with measurable disease at baseline (41%; 95% CI 35.9–45.8) in the RIB arm and 52/181 (29%; 95% CI 22.1–35.3) in the PBO arm had a complete or partial response (P=0.003). The probability of a response by 6 months (RIB vs PBO arm) was 27% (95% CI 22.7–31.0) vs 16% (95% CI 12.0–21.6). At Week 8, a decrease from baseline in target lesion(s) size per RECIST was observed in (RIB vs PBO) 232/484 (48%) vs 92/242 (38%; P=0.006). A decrease in best % change from baseline in target lesion(s) size per RECIST was reported in 79% of 344 pts in the RIB arm and 66% of 166 pts in the PBO arm. At Cycle 3 Day 1 (Week 8), the absolute mean change from baseline in EORTC QLQ-C30 pain score was similar in both arms: –4.2 RIB (n = 361); –2.9 PBO (n = 169; P=0.517).Table: 331P
|2L setting||Early relapse setting|
Relapse >12 months from (neo)adjuvant endocrine therapy and subsequent progression on endocrine therapy for ABC
ABC at diagnosis that progressed after 1 line of endocrine therapy for ABC
|Relapse on or ≤ 12 months after (neo)adjuvant endocrine therapy with no treatment for ABC|
|RIB + FUL||PBO + FUL||RIB + FUL||PBO + FUL|
|Median PFS, months||18.8||11.4||13.1||8.6|
|Hazard ratio (95% CI)||0.539 (0.333–0.873)||0.591 (0.422–0.830)|
RIB + FUL consistently prolonged PFS in the separate 2L and early relapse settings. In the full population, RIB + FUL demonstrated early tumor size reduction and a higher response rate vs PBO + FUL, consistent with other RIB studies. Pain reduction was similar in both arms, suggesting addition of RIB to FUL does not negatively affect HRQoL.
Clinical trial identification
NCT02422615 April 21, 2015.
Legal entity responsible for the study
Novartis Pharmaceuticals Corporation.
Novartis Pharmaceuticals Corporation.
Editorial assistance was provided by Cassandra Krone PhD of ArticulateScience Ltd.
G. Jerusalem: Grants and personal fees: Novartis, during the conduct of the study; Grants, personal fees and non-financial support: Novartis, Roche; Personal fees and non-financial support: Lilly, Celgene, BMS; Grants and personal fees: Amgen; Personal fees: Pfizer, Puma, Daiichi-Sankyo; Grants from MSD; Personal fees and non-financial support: AstraZeneca, outside the submitted work. P.A. Fasching: Grants and personal fees: Novartis; Personal fees: Roche, Pfizer, Celgene, Teva, during the conduct of the study. M. Martín: Consulting/advisory role and research funding: Novartis, Roche/Genentech; Consulting/advisory role funding: Lilly; Consulting/advisory role funding: Pfizer, during the conduct of the study. K. Petrakova: Consulting/advisory role, Speaker's bureau, Travel/accommodation/expenses: Roche, Pfizer, Novartis, during the conduct of the study. G.S. Sonke: Institutional reimbursement for patient accrual: Novartis, during the conduct of the study; Institutional reimbursement for education and steering committee activities: Novartis; Institutional research support: Merck, AstraZeneca, Roche, outside the submitted work. E. Vagnon, J. Alam: Employment with Novartis. O. Kong, D. Chandiwana: Employment and stock ownership: Novartis. M. De Laurentiis: Grants and personal fees: Novartis, during the conduct of the study; Grants and personal fees: Pfizer, Roche, Astra Zeneca, Amgen; Grants: MSD, outside the submitted work.