LBA7_PROverall survival (OS) results of the phase III MONALEESA-3 trial of postmenopausal patients (pts) with hormone receptor-positive (HR+), human epidermal growth factor 2-negative (HER2−) advanced breast cancer (ABC) treated with fulvestrant (FUL) ± ribociclib (RIB)

Abstract Background The phase III MONALEESA-3 trial (NCT02422615; N = 726) investigated RIB, a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor, + FUL as first-line (1L) or second-line (2L) treatment for postmenopausal pts with HR+/HER2− ABC. Here we report OS and 1L progression-free survival (PFS) results. Methods Postmenopausal pts with HR+/HER2− ABC were randomized 2:1 to receive RIB + FUL or PBO + FUL in 1L and 2L settings. This is the 2nd of 3 protocol-specified OS analyses. Results At the data cutoff (3 Jun 2019), 153 pts were still on treatment (RIB, n = 121 [25.0%]; PBO, n = 32 [13.2%]); OS was evaluated after 275 deaths (RIB, 167 [34.5%]; PBO, 108 [44.6%]). Median follow-up was 39.4 mo. RIB + FUL demonstrated a statistically significant OS prolongation over PBO + FUL (median, NR vs 40.0 mo; HR, 0.724, 95% CI, 0.568-0.924, P = 0.00455). The result crossed the prespecified Lan DeMets (O’Brien Fleming) stopping boundary (P = 0.01129) for superior efficacy. Per protocol, these OS results will be considered final. OS benefit with RIB vs PBO was consistent across all subgroups, including the 1L subgroup (median, NR vs 45.1 mo; HR, 0.700 [95% CI, 0.479-1.021]) and the early-relapse/2L subgroup (median, 40.2 vs 32.5 mo; HR, 0.730 [95% CI, 0.530-1.004]). In pts receiving 1L treatment, the median PFS (descriptive analysis) with RIB + FUL vs PBO + FUL was 33.6 vs 19.2 mo (HR, 0.546 [95% CI, 0.415-0.718]). Time to progression on next-line therapy or death (PFS2) was also longer with RIB vs PBO (median, 39.8 vs 29.4 mo; HR, 0.670 [95% CI, 0.542-0.830]). The safety profile was consistent with previously published analyses. Conclusions There was a statistically significant OS prolongation with RIB over PBO, which was consistent across all subgroups. The median PFS with RIB in the 1L setting is the longest reported in a phase III trial in HR+/HER2− ABC. These data, combined with results from MONALEESA-7, confirm RIB benefit with multiple combination partners in pre- and postmenopausal pts, and support RIB as a recommended CDK4/6 inhibitor as 1L and 2L treatment in pts with HR+/HER2- ABC. Clinical trial identification NCT02422615. Editorial acknowledgement Editorial assistance in the writing was provided by Tara Wabbersen, PhD, of MediTech Media, LLC, through funding by Novartis Pharmaceuticals Corporation. Legal entity responsible for the study Novartis Pharmaceuticals Corporation. Funding Novartis Pharmaceuticals Corporation. Disclosure D.J. Slamon: Leadership role, Travel / Accommodation / Expenses: Biomarin; Research grant / Funding (self), Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options: Pfizer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Novartis; Advisory / Consultancy: Eli Lilly. S. Chia: Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Advisory / Consultancy, Research grant / Funding (institution): Hoffman-La Roche; Advisory / Consultancy, Research grant / Funding (institution): Eli Lilly. P.A. Fasching: Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Celgene; Honoraria (self), Advisory / Consultancy: Daiichi Sankyo; Honoraria (self), Advisory / Consultancy: Eisai; Honoraria (self), Advisory / Consultancy: Hexal; Honoraria (self), Advisory / Consultancy: Merck Sharp & Dohme; Honoraria (self), Advisory / Consultancy: Myelo Therapeutics GmbH; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Novartis; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: Puma Biotechnology; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Teva; Research grant / Funding (institution): BioNTech AG. M. De Laurentiis: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Celgene; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Eisai; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Eli Lilly; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Amgen. S. Im: Research grant / Funding (self): AstraZeneca; Advisory / Consultancy: Novartis; Advisory / Consultancy: Hanmi; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Eisai. K. Petrakova: Honoraria (self), Travel / Accommodation / Expenses: Roche; Honoraria (self), Travel / Accommodation / Expenses: Novartis; Honoraria (self), Travel / Accommodation / Expenses: BMS. F.J. Esteva: Advisory / Consultancy, Research grant / Funding (self): Novartis; Advisory / Consultancy, Research grant / Funding (self): Pfizer; Advisory / Consultancy, Research grant / Funding (self): Genentech/Roche; Advisory / Consultancy: Celltrion Healthcare ; Advisory / Consultancy: Seattle Genetics; Research grant / Funding (self): GlaxoSmithKline. M. Martin: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Lilly; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Novartis; Honoraria (self), Advisory / Consultancy: Roche-Genentech; Honoraria (self), Advisory / Consultancy: GlaxoSmithKline; Honoraria (self), Advisory / Consultancy: Pharmamar; Honoraria (self), Advisory / Consultancy: Taiho Oncology ; Research grant / Funding (self): Roche. A. Nusch: Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Novartis; Advisory / Consultancy: Amgen. G.S. Sonke: Honoraria (institution), Research grant / Funding (institution), institutional reimbursement for patient accrual; institutional reimbursement for education and steering committee activities: Novartis; Research grant / Funding (institution): Merck; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Roche. J.T. Beck: Research grant / Funding (institution): Novartis . M. Sondhi: Shareholder / Stockholder / Stock options, Full / Part-time employment: Novartis Pharmaceuticals Corporation. Y. Wang: Shareholder / Stockholder / Stock options, Full / Part-time employment: Novartis Pharmaceuticals Corporation. A. Chakravartty: Shareholder / Stockholder / Stock options, Full / Part-time employment: Novartis Pharmaceuticals Corporation. K. Rodriguez-Lorenc: Shareholder / Stockholder / Stock options, Full / Part-time employment: Novartis Pharmaceuticals Corporation. G. Jerusalem: Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (self), Advisory / Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Lilly; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Roche; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Celgene; Advisory / Consultancy: Daiichi Sankyo; Advisory / Consultancy: Puma Biotechnology. All other authors have declared no conflicts of interest.