Abemaciclib plus fulvestrant for HR+, HER2- advanced breast cancer following progression on a prior CDK4/6 inhibitor plus endocrine therapy: Subgroup analyses from the phase III postMONARCH trial

BackgroundCDK4/6 inhibitors (CDK4/6i) + endocrine therapy (ET) are standard first line (1L) treatment for HR+, HER2- advanced breast cancer (ABC), but optimal therapy after disease progression is unclear. The Phase 3 postMONARCH study demonstrated a statistically significant progression-free survival (PFS) improvement with the addition of abemaciclib to fulvestrant in patients (pts) with HR+, HER2- ABC and disease progression on prior CDK4/6i + ET (HR 0.73; 95% CI 0.57- 0.95). Here we report PFS in clinically relevant subgroups.MethodspostMONARCH was a global, double-blind, placebo-controlled study, randomizing pts 1:1 to abemaciclib + fulvestrant or placebo + fulvestrant, stratified by geography, visceral metastases and duration of prior CDK4/6i. Eligible pts had disease progression on 1L CDK4/6i + AI or relapse on/after adjuvant CDK4/6i + ET and no prior fulvestrant or chemotherapy for ABC. PFS analyses of clinically relevant subgroups were assessed using Kaplan-Meier method, including presence of liver metastases, measurable or bone-only disease, and key biomarkers.ResultsOverall, 368 pts were randomized to abemaciclib + fulvestrant (n=182) or placebo + fulvestrant (n=186); 139 pts (38%) had liver metastases, 258 (70%) had measurable disease, and 74 (20%) had bone-only disease. Most pts (99%) received prior CDK4/6i for ABC (median duration 20.1 months) and predominantly (59%) with palbociclib. Among ctDNA evaluable pts (320, 87%), 45% had an ESR1 mutation and 49% had a PI3K pathway alteration detected at baseline. PFS benefit was generally consistent across clinical subgroups and will be presented, along with PFS analyses of key biomarker subgroups. Table: 351P Patients N Events Median PFS (95% CI) HR (95% CI) Abemaciclib + Fulvestrant Placebo + Fulvestrant All 368 258 6.0 (5.6, 8.6) 5.3 (3.7, 5.6) 0.73 (0.57, 0.95) Liver Metastases Yes 139 115 4.1 (3.7, 5.7) 1.9 (1.9, 3.7) 0.63 (0.44, 0.91) No 229 143 9.1 (5.8, 11.1) 5.8 (5.4, 7.7) 0.78 (0.56, 1.09) Measurable Disease Yes 258 192 5.6 (3.8, 6.8) 3.7 (3.0, 5.3) 0.72 (0.54, 0.95) No 110 66 9.3 (6.3, NR) 7.6 (5.4, 10.3) 0.71 (0.44, 1.16) Bone-Only Disease Yes 74 46 15.1 (6.3, NR) 6.2 (5.4, 9.9) 0.51 (0.28, 0.95) No 294 212 5.6 (4.0, 7.1) 3.9 (3.6, 5.4) 0.78 (0.59, 1.02) NR = not reached ConclusionsPFS analyses of clinically relevant subgroups showed a consistent benefit of abemaciclib + fulvestrant after progression on prior CDK4/6i + ET.Clinical trial identificationNCT05169567.Legal entity responsible for the studyEli Lilly and Company.FundingEli Lilly and Company.DisclosureG. Bianchini: Financial Interests, Personal, Advisory Board: AstraZeneca, Daiichi Sankyo, Lilly, Novartis, Pfizer, Roche, Amgen, MSD, Chugai, EISAI, Gilead, Seagen, Exact Science, Roche, MSD, Gilead, Lilly, Menarini Stemline; Financial Interests, Personal, Other, Consultancy: AstraZeneca, Daiichi Sankyo, Roche, MSD, Gilead, Sanofi, Seagen; Financial Interests, Personal, Invited Speaker: Lilly, Roche, AstraZeneca, Daiichi Sankyo, MSD, Chugai, EISAI, Gilead, Seagen, Neopharm Israel, Daiichi Sankyo, Gilead; Financial Interests, Personal, Other, Support for attending meetings and/or travel: Roche, Pfizer, MSD, Chugai, Novartis, Gilead, Daiichi Sankyo; Financial Interests, Institutional, Other, Research Grant: Gilead; Financial Interests, Personal and Institutional, Steering Committee Member: Roche, Novartis, Lilly, AstraZeneca; Financial Interests, Institutional, Local PI: Gilead, Pfizer, Daiichi Sankyo, Lilly, MSD, Novartis; Non-Financial Interests, Leadership Role, Head of Traslational Research: Fondazione Michelangelo; Non-Financial Interests, Other, Scientific Board Member: Fondation ARC, Fondazione Umberto Veronesi; Non-Financial Interests, Member: AIOM. M. Martin Jimenez: Financial Interests, Personal, Advisory Board: Astrazeneca, Lilly, Roche/Genentech, Daiichi Sankyo, Menarinio-Stemline; Financial Interests, Personal, Invited Speaker: Pfizer, Astrazeneca, Lilly, Novartis, Roche/Genentech; Financial Interests, Institutional, Research Grant: Novartis, Roche, Puma; Non-Financial Interests, Member of Board of Directors: TRIO; Non-Financial Interests, Leadership Role: Geicam; Non-Financial Interests, Member: ASCO; Non-Financial Interests, Advisory Board: SEOM. S. Graff: Financial Interests, Personal, Advisory Board: Pfizer, Seagen, Novartis, AstraZeneca, Genentech, Lilly, Gilead Sciences, Daiichi Sankyo, Menarini; Financial Interests, Personal, Invited Speaker: The Academy for Healthcare Learning, DAVA Oncology, MJH Life Sciences, MedIQ, Medical Educator Consortium, IntegrityCE, Research to Practice; Financial Interests, Personal, Writing Engagement: MedPage Today, WebMD/Medscape; Financial Interests, Personal, Full or part-time Employment: Dr Susan Love Foundation for Breast Cancer Research; Financial Interests, Personal, Stocks/Shares: HCA Healthcare; Financial Interests, Personal and Institutional, Steering Committee Member: Daiichi Sankyo, Novartis, AstraZeneca. R. Jeselsohn: Financial Interests, Personal, Advisory Board: Pfizer, Lilly, Astra Zenenca, Novartis, Carrick Therapeutics; Financial Interests, Institutional, Funding: Lilly, Pfizer. S. Wander: Financial Interests, Advisory Board: Foundation Medicine, Eli Lilly, Novartis, AstraZeneca, Puma Biotechnology, Hologic, Biovica, Genentech; Other, Advisory Board: Pfizer; Other, Speaker, Consultant, Advisor: 2ndMD, Guardant Health, Eli Lilly; Financial Interests, Research Funding: Genentech, Eli Lilly, Pfizer, Sermonix, Nuvation Bio, Regor Therapeutics. R. Layman: Financial Interests, Personal, Advisory Board: Eli Lilly, Novartis, Celcuity, Gilead Sciences, BioTheryx; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Writing Engagement: Pfizer; Financial Interests, Institutional, Local PI: Accutar Biotechnology, Eli Lilly, Pfizer, Celcuity; Financial Interests, Personal, Steering Committee Member: Eli Lilly, Celcuity; Financial Interests, Institutional, Research Grant, Supply of drug for clinical trial: Novartis, Puma; Financial Interests, Institutional, Research Grant: Celcuity; Financial Interests, Institutional, Trial Chair: Arvinas. S.A. Hurvitz: Financial Interests, Personal, Invited Speaker: Clinical Care Options, axis medical, cancer expert now, ICHE, MJH Associates, PER, Primo, Projects in Knowledge, Prova Education, Research to Practice, Ultimate Medical Academy, Vaniam, WebMD, Peer Education, PrecisCA, Peer Voice, Curio, Reach MD/MedIQ, Imedex, MD Outlook, Prime Oncology, Reach MD, OncLive; Financial Interests, Personal, Stocks/Shares, spouse owns: ROM Tech; Financial Interests, Personal, Royalties, author medical book: McGraw; Financial Interests, Personal, Royalties: Elsevier, Springer, Sage, Wolters Kluwer, Wiley; Financial Interests, Institutional, Local PI: Ambrx, AstraZeneca, Arvinas, Genentech/Roche, Gilead, GSK, Immunomedics, Eli Lilly, Macrogenics, Novartis, Pfizer, OBI Pharma, Pieris, PUMA, Radius, sanofi, Seattle Genetics, Dignitana, Zymeworks, Phoenix Molecular Designs, Ltd, cytomx, Dantari, G1 Therapeutics, Greenwich Life Sciences, Loxo Oncology, orinove, Orum; Financial Interests, Institutional, Coordinating PI: Daiichi Sankyo, Celcuity; Financial Interests, Institutional, Research Grant: Ambrx; Financial Interests, Steering Committee Member: Greenwich Life Sciences, Orum; Non-Financial Interests, Advisory Role: Daiichi Sankyo, Novartis, Ambrx, 4DPharma, Dantari, Macrogenics, Lilly, Artios, Roche, Pyxis, Amgen, Pieris, Arvinas, Immunomedics/Gilead, Briacell, Jazz Pharmaceuticals, Boehringer Ingelheim, Stemline/Menarini; Non-Financial Interests, Principal Investigator: Daiichi Sankyo, Genentech, Seattle Genetics; Non-Financial Interests, Member: ASCO, AACR; Non-Financial Interests, Other, speaker: National Breast Cancer Coalition; Non-Financial Interests, Member, site representative for breast cancer guidelines: National Comprehensive Cancer Network. E.P. Hamilton: Financial Interests, Institutional, Other, Consulting/Advisory Role: Genentech/Roche, Novartis, Lilly, Pfizer, Mersana, Olema Pharmaceuticals, Stemline Therapeutics, AstraZeneca, Daiichi Sankyo, Ellipses Pharma, Tubulis, Verascity Science, Theratechnologies; Financial Interests, Institutional, Other, Consulting: Accutar Biotechnology, Entos, Fosun Pharma, Gilead Sciences, Jazz Pharmaceuticals, Jefferies LLC, Medical Pharma Services, Tempus Labs, Zentalis Pharmaceuticals; Financial Interests, Institutional, Research Grant: Oncomed, Genentech/Roche, Zymeworks, Rgenix, Arqule, Clovis, Millennium, Acerta Pharma, Sermonix Pharmaceuticals, Black Diamond, Karyopharm, Curis, Syndax, Novartis, Boehringer Ingelheim, Immunomedics, FujiFilm, Taiho, Deciphera, Molecular Templates, Dana Farber Cancer Inst, Hutchinson MediPharma, MedImmune, Seagen, Compugen, TapImmune, Lilly, Pfizer, H3 Biomedicine, Merus, Regeneron, Arvinas, StemCentRx, Verastem, eFFECTOR Therapeutics, CytomX, InventisBio, Lycera, Mersana, Radius Health, Abbvie, Nucana, Leap Therapeutics, Zenith Epigenetics, Harpoon, Orinove, AstraZeneca, Tesaro, Macrogenics, EMD Serono, Daiichi Sankyo, Syros, Sutro, G1 Therapeutics, PharmaMar, Olema, Immunogen, Plexxicon, Amgen, Akesobio Australia, Shattuck Labs, ADC Therapeutics, Aravive, Atlas MedX, Ellipses Pharma, Incyte, Jacobio, Mabspace Biosciences, ORIC Pharmaceuticals, Pieris Pharmaceuticals, Pionyr Immunotherapeutics, Repertoire Immune Medicine, Treadwell Therapeutics, Accutar Biotechnology, Artios, BeiGene, Bliss BioPharmaceuticals, Cascadian Therapeutics, Context Therapeutics, Cullinan, Dantari, Duality Biologics, Elucida Oncology, Infinity Pharmaceuticals, K-Group Beta, Kind Pharmaceuticals, Loxo Oncology, Oncothyreon, Orum Therapeutics, Prelude Therapeutics, Profound Bio, Relay Therapeutics, Tolmar, Torque Therapeutics; Financial Interests, Institutional, Local PI: Bristol-Myers Squibb, Eisai, Fochon Pharmaceuticals, Gilead Sciences, Inspirna, Myriad Genetic Laboratories, Silverback Therapeutics, Stemline Therapeutics. 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Zhou: Financial Interests, Personal, Full or part-time Employment: Eli Lilly and Company. E. Ravenberg: Financial Interests, Personal, Full or part-time Employment: Eli Lilly and Company. L. Litchfield: Financial Interests, Personal, Full or part-time Employment: Eli Lilly and Company. K. 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