LBA4 - Updated overall survival (OS) results from the first-line (1L) population in the Phase III MONALEESA-3 trial of postmenopausal patients (pts) with HR+/HER2? advanced breast cancer (ABC) treated with ribociclib (RIB) + fulvestrant (FUL)

Background

The MONALEESA-3 (NCT02422615) final protocol-specified OS analysis and an exploratory OS analysis with extended follow-up demonstrated significant OS benefit with RIB + FUL vs placebo (PBO) + FUL as 1L or second-line (2L) treatment (tx). At the time of these analyses, the median (m) OS was 53.7 vs 41.5 mo for RIB vs PBO in the intent-to-treat (ITT) population. Although the mOS was not reached in the RIB arm for 1L pts, the mOS in 2L pts was 39.7 vs 33.7 mo for RIB vs PBO. We report an exploratory analysis of OS with additional follow-up, allowing further characterization of long-term OS benefits of RIB in the 1L setting.

Methods

Postmenopausal pts with HR+/HER2− ABC were randomized 2:1 to receive RIB + FUL or PBO + FUL. Updated OS in the 1L setting (pts with de novo disease or relapse >12 mo from completion of [neo]adjuvant endocrine therapy) was assessed by Cox proportional hazards model and Kaplan-Meier methods. Progression-free survival 2 (PFS2) and chemotherapy-free survival (CFS) were also evaluated.

Results

At the data cutoff (January 12, 2022), the median follow-up for 1L pts was 70.8 mo; 16.5% and 8.6% of pts remained on tx in the RIB and PBO arms, respectively. An OS benefit was observed with 1L RIB vs PBO (mOS, 67.6 vs 51.8 mo; HR, 0.67; 95% CI, 0.50-0.90). The OS rate at 5 years was 56.5% vs 42.1% for RIB vs PBO, respectively. PFS2 (HR, 0.64) and CFS (HR, 0.62) favored RIB vs PBO. In pts who discontinued study tx, 81.8% and 89.7% received subsequent antineoplastic therapy, while 16.7% vs 35.0% received a subsequent cyclin-dependent kinase 4/6 inhibitor in the RIB vs PBO arms. Results in the ITT and 2L populations were generally consistent with the previous analysis.

Conclusions

This exploratory analysis of 1L RIB + FUL in MONALEESA-3 reports the longest mOS thus far (67.6 mo—a 15.8-mo improvement vs PBO and a relative reduction in risk of death of 33%) in a 1L population in a Phase III clinical trial in ABC. These impressive results in the 1L setting further support the use of RIB + ET in HR+/HER2− ABC.

Clinical trial identification

NCT02422615.

Editorial acknowledgement

Medical writing support was provided by Casey Nielsen at MediTech Media, funded by Novartis Pharmaceuticals Corporation.

Legal entity responsible for the study

Novartis Pharmaceuticals Corporation.

Funding

Novartis Pharmaceuticals Corporation.

Disclosure

P.A. Fasching: Financial Interests, Personal, Invited Speaker: Novartis, Pfizer, Daiichi Sankyo, AstraZeneca, Eisai, Merck Sharp & Dohme, Lilly, Seagen, Roche, Gilead; Financial Interests, Personal, Advisory Board: Novartis, Pfizer, Daiichi Sankyo, AstraZeneca, Eisai, Merck Sharp & Dohme, Lilly, Pierre Fabre, Seagen, Roche, Hexal, Agendia, Sanofi Aventis, Gilead; Financial Interests, Institutional, Funding, Institutional Funding: Biontech, Cepheid; Financial Interests, Personal, Research Grant: Pfizer. S. Chia: Financial Interests, Personal, Advisory Board: Novartis, Pfizer, Hoffman La Roche, Eli Lilly; Financial Interests, Institutional, Funding, My institution received funds for participation in clinical trials by: Novartis, Pfizer, Hoffman La Roche, Eli Lilly. G. Jerusalem: Financial Interests, Personal, Other, Grants, Personal Fees & Non-Financial Support: Novartis, Roche, Pfizer; Financial Interests, Personal, Other, Personal Fees & Non-Financial Support: Lilly, Amgen, BMS, AstraZeneca; Financial Interests, Personal, Other, Personal Fees: AbbVie, Daiichi Sankyo, Seagen; Non-Financial Interests, Personal, Other, Non-Financial Support: Medimmune, Merck KGaA. M. De Laurentiis: Financial Interests, Personal, Speaker’s Bureau, Speaker's Honoraria: Pfizer, Novartis, Roche, AstraZeneca, Eisai, Eli Lilly, Pierre Fabre; Financial Interests, Personal, Advisory Board, Advisory Board Honoraria: Pfizer, Novartis, Roche, AstraZeneca, Eisai, Eli Lilly, MSD, Pierre Fabre. S. Im: Financial Interests, Personal, Research Grant: AstraZeneca; Financial Interests, Personal, Advisory Board: AstraZeneca, Hanmi, Pfizer, Novartis; Non-Financial Interests, Personal, Other, Travel support: Novartis; Financial Interests, Personal, Advisory Role, Participation in advisory meetings: Eisai, Amgen, Roche, Lilly, GSK, MSD; Financial Interests, Personal, Other: Daewoong Pharm. K. Petrakova: Financial Interests, Personal, Advisory Board: Novartis, AstraZeneca, Roche, Pfizer. G.V. Bianchi: Financial Interests, Personal, Advisory Role: Roche, Eli Lilly, Novartis, Seagen, AstraZeneca/Daichi Sankyo, MSD. M. Martin Jimenez: Financial Interests, Personal, Speaker’s Bureau, Speaker Honoraria: Lilly, Pfizer; Financial Interests, Personal, Advisory Board, Honoraria for Participation in Advisory Boards: Lilly, Pfizer, AstraZeneca, Novartis, Roche-Genentech, GlaxoSmithKline, PharmaMar, Taiho Oncology; Financial Interests, Personal, Research Grant: Novartis, Roche-Genentech. A. Nusch: Financial Interests, Personal, Advisory Role, Consulting/Advisory role: Novartis, Amgen; Financial Interests, Personal, Funding, Research Funding: Novartis; Other, Personal, Travel/Accommodation/Expenses: Novartis; G.S. Sonke: Financial Interests, Institutional, Other, Institutional Reimbursement for Patient Accrual: Novartis; Financial Interests, Institutional, Other, Institutional Reimbursement for Education and Steering Committee Activities: Novartis; Financial Interests, Institutional, Other, Institutional research support: Merck, AstraZeneca, Roche. J.T. Beck: Financial Interests, Institutional, Research Grant, Institutional funding for doing research: AbbVie, Alliance, Argenx, Ascentage Pharma Group, AstraZeneca, Biodesix, Bio-Thera, Bristol Myers Squibb, Celgene, Eli Lilly, Genentech-Roche, Hutchison, Immunomedics, Gilead, MT Group Merck, Nektar, Pfizer, Polynoma, Seattle Genetics, Serono-EMD, Tesaro, TG Therapeutics, Daiichi Sankyo, Exact Sciences, Boehringer Ingelheim, Laekna, Novocure, Mirati Therapeutics, Tarveda Therapeutics, Sumitomo Dainippon Pharma Oncology (formerly Boston Bio), Elpiscience Biopharma, Takeda, Vaccinex, Vincerx Pharma, Ultimovacs, Mersana. J.P. Zarate, Y. Wang, A. Chakravartty, C. Wang: Financial Interests, Personal, Full or part-time Employment: Novartis; Financial Interests, Personal, Stocks/Shares: Novartis. D. Slamon: Non-Financial Interests, Personal, Member of the Board of Directors: Biomarin; Non-Financial Interests, Personal, Other, Travel expenses: Biomarin, Pfizer, Novartis; Financial Interests, Personal, Stocks/Shares: Pfizer, Amgen, Seattle Genetics; Financial Interests, Personal, Other, Research funding: Pfizer, Novartis; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Other, Consulting: Novartis, Eli Lilly. All other authors have declared no conflicts of interest.