MONARCH 2 led to abemaciclib + fulvestrant approval in pts with HR+, HER2- ABC with disease progression on prior endocrine therapy and demonstrated significant OS benefit. MONARCH 3 led to abemaciclib + NSAI approval as initial therapy in postmenopausal pts with HR+, HER2- ABC with significant improvement in progression-free survival (PFS). Here we report the second interim analysis (IA2) OS results for MONARCH 3, an analysis included in the European Product Label by request of EMA.

MONARCH 3 is a 2:1 randomized, double-blind, placebo-controlled Phase 3 study of NSAI +/- abemaciclib. Detailed study information, including the primary endpoint of PFS are published (Goetz, JCO 2017). OS is a key secondary endpoint and this prespecified OS IA2 (data cut 2 Jul 2021) was scheduled after ∼252 events in the ITT population (80% of planned events for final OS analysis), using a stratified log-rank test and applying a pre-defined error spending strategy to assess significance in both the ITT and the subgroup with visceral disease (sVD).

493 pts were randomized to receive NSAI + abemaciclib (n=328) or placebo (n=165). At IA2, with 70.2 months median follow-up, in the ITT the median OS (mOS) was 67.1 months for abemaciclib + NSAI vs 54.5 months for placebo + NSAI (HR=0.754, 95% CI: 0.584-0.974, 2-sided p=0.0301). In sVD, the mOS was 65.1 months for abemaciclib + NSAI vs 48.8 months for placebo + NSAI (HR=0.708, 95% CI: 0.508-0.985; 2-sided p=0.0392). According to the alpha spending procedure, the critical boundaries for declaring significance in both groups were not met for IA2. Follow-up is ongoing for final OS analysis (expected 2023). Safety data were consistent with the known profile of abemaciclib.

In the second interim prespecified overall survival analysis from MONARCH 3, longer OS was observed in both the ITT and sVD (an increase in the median OS by >12 months with the addition of abemaciclib to NSAI), however neither met the threshold for formal statistical significance according to the alpha spend procedure. Final OS analysis is planned when at least 315 OS events in ITT and 189 in sVD are observed.

NCT02246621.

Trish Huynh, employee of Eli Lilly and Company (Indianapolis, IN) provided medical writing support.

Eli Lilly and Company.

Eli Lilly and Company.

M.P. Goetz: Other, Personal, Other: Genomic Health; Financial Interests, Institutional, Other, consulting fees to Mayo: Eli Lilly and Company; Other, Institutional, Other, consulting fees to Mayo: Biovica, Novartis, Sermonix, Context Pharm, Pfizer, AstraZeneca, Eagle Pharmaceuticals; Financial Interests, Institutional, Research Grant: Pfizer, Eli Lilly and Company, Sermonix; Other, Institutional, Advisory Board, Honoraria to Mayo: ARC Therapeutics, Blueprint Medicines, Sanofi Genzyme, Biotheranostics; Financial Interests, Personal, Other, CME presentation: Research to Practice, Clinical Education Alliance, Medscape; Financial Interests, Personal, Other, Session moderator: Curio; Financial Interests, Personal, Other, Honoraria to Mayo: Total Health Conferencing. M. Toi: Financial Interests, Personal, Research Grant, Lecture Honoraria: Chugai, Takeda, Pfizer, Taiho, Eisai, AstraZeneca, Shimadzu, Yakult; Other, Personal, Other, Manuscript Fee: Kyowa-Kirin; Financial Interests, Research Grant: JBCRG association, Astellas, AFI technologies, Shionogi, GL Science, KBCRN association; Financial Interests, Personal, Other, Research grant, Lecture honoraria, Advisory role for a drug development: Daiichi-Sankyo; Financial Interests, Personal, Research Grant, Lecture Honoraria, An advisory role: Eli Lilly and Company; Other, Personal, Other, Lecture Honoraria: MSD, Exact Science, Novartis; Other, Other, Honoraria for an advisory meeting: BMS; Financial Interests, Personal, Other, Research fund and honoraria for lecture: Nippon Kayaku; Other, Advisory role: Athenex Oncology, Bertis, Terumo, Kansai Medical Net; Financial Interests, Other, Advisory role, research grant: Luxonus; Other, Member of the Board of Directors: JBCRG association, Organization for Oncology and Translational Research, Kyoto Breast Cancer Research Network. J. Huober: Financial Interests, Personal, Other, Grant: Eli Lilly and Company, Novartis, Celgene; Financial Interests, Personal, Other, Travel expenses: Roche, Pfizer; Other, Personal, Other: Gilead; Financial Interests, Personal, Other: Daiichi Sankyo, AstraZeneca, Seagen, MSD, AbbVie; Financial Interests, Other, Grant: Hexal. J. Sohn: Financial Interests, Institutional, Research Grant: MSD, Roche, Novartis, AstraZeneca, Eli Lilly and Company, Pfizer, GSK, Daiichi Sankyo, Sanofi, Boehringer Ingelheim. O. Tredan: Non-Financial Interests, Personal, Other: Eli Lilly and Company, Roche, Novartis-Sandoz, AstraZeneca, Pfizer; Non-Financial Interests, Personal, Other, Grant: MSD; Financial Interests, Other, Grant: BMS; Other, Personal, Other: Pierre Fabre, Eisai, Seagen, Daiichi-Sankyo, Stemline, Gilead. M. Campone: Financial Interests, Institutional, Research Grant: Pfizer, AstraZeneca, Sanofi, Pierre Fabre, Takeda, AbbVie, Servier, Sandoz, Accord; Financial Interests, Personal, Other, Speaker fees: Novartis, Eli Lilly and Company. S. Paluch-Shimon: Other, Research Grant: Pfizer; Other, Speaker’s Bureau, Honoraria, Consultancy: Roche, AstraZeneca, Novartis, Pfizer, Exact Sciences. G. van Hal: Financial Interests, Personal, Stocks/Shares: Eli Lilly and Company; Financial Interests, Personal, Other, Employee: Eli Lilly and Company. A. Shahir: Financial Interests, Personal, Stocks/Shares: Eli Lilly and Company; Financial Interests, Personal, Other, Employee: Eli Lilly and Company. H. Iwata: Financial Interests, Other, Honoraria: Daiichi Sankyo, Chugai, AstraZeneca, Eli Lilly and Company, MSD, Pfizer; Financial Interests, Advisory Role: Daichi-Sankyo, Chugai, Pfizer, Sanofi, Lilly, MSD, Pfizer, Novartis; Financial Interests, Research Grant: Daiichi-Sankyo, Chugai, AstraZeneca, Lilly, MSD, Pfizer, Novartis, Amgen. S. Johnston: Financial Interests, Personal, Other, Consulting/Advisory Role: Eli Lilly, Puma Biotechnology; Financial Interests, Personal, Other, Consulting/Advisory Role and Speakers Bureau: AstraZeneca, Pfizer, Novartis; Financial Interests, Personal, Other, Speakers Bureau: Eisai, Roche/Genentech; Financial Interests, Institutional, Funding, Research funding for lab studies and clinical trials: Pfizer; Financial Interests, Institutional, Funding, Research funding for lab studies: Puma Biotechnology; Financial Interests, Institutional, Funding, Research funding for clinical trials: Eli Lilly, AstraZeneca, Novartis, Roche/Genentech. All other authors have declared no conflicts of interest.