Abstract 220P
Background
METALLICA showed that metformin reduced the incidence and severity of ALP-induced hyperglycemia in HR+/HER2-/PIK3CA-mutated ABC pts treated with ALP+ET. The EMERALD study identified early progressions (<12 months [mo]) on previous CDK4/6i therapy for ABC as a strong predictor of resistance to ET. Here, we examine the impact that TTP on prior CDK4/6i has on the efficacy of ALP+ET.
Methods
The METALLICA (NCT04300790) trial has been previously reported (Ruiz-Borrego et al., Cancer Res, 2023). Briefly, pts with HR+/HER2-/PIK3CA-mutated ABC who progressed on an aromatase inhibitor-containing regimen and who were treated with ≤2 prior lines of ET and ≤1 of prior chemotherapy for ABC were eligible. ALP (oral, 300 mg QD) was administered with ET (physician's choice; fulvestrant, letrozole, or exemestane) in 28-day cycles. This analysis retrospectively compared PFS according to TTP on the prior CDK4/6i-based regimen (<12 vs. ≥12 mo). The Cox regression model was adjusted by age, ECOG performance status, number and location of metastatic disease, number of prior lines for ABC, and type of CDK4/6i.
Results
Between 30 August 2020 and 10 March 2022, 68 pts with HR+/HER2-/PIK3CA-mutated ABC were enrolled. Median age was 55.0 (range, 29–79) years and 63 pts (92.6%) received fulvestrant as ET. A total of 58 pts (85.3%) were previously treated with CDK4/6i therapy for ABC, all in the line immediately prior to start of this study. A total of 23 pts (39.6%) had a TTP on previous CDK4/6i-based regimen <12 mo. Median follow-up was 7.8 mo. Median PFS was 7.3 mo for all CDK4/6i-treated pts. Among pts with prior exposure to CDK4/6i ≥12 mo, ALP+ET achieved a median PFS of 11.1 mo vs. 2.8 mo from pts with a TTP on previous CDK4/6i therapy of <12 mo (HR=0.28; 95%CI: 0.11-0.73, p=0.009).
Conclusions
These data suggest that duration of prior CDK4/6i exposure may be associated with PFS in HR+/HER2-/PIK3CA-mutated ABC pts treated with ALP+ET. Progression within the 1st year of prior CDK4/6i-based regimen seems to be prognostic of less favorable outcomes.
Legal entity responsible for the study
Medica Scientia Innovation Research (MEDSIR).
Funding
Has not received any funding.
Disclosure
A. Llombart-Cussarc: Financial Interests, Personal, Research Grant: Roche, Agendia, Lilly, Pfizer, Novartis, Merck Sharp & Dome, Gilead, Daiichi Sankyo; Financial Interests, Personal, Advisory Role: Lilly, Roche, Pfizer, Novartis; Financial Interests, Personal, Speaker’s Bureau: Lilly, AstraZeneca, Merck Sharp & Dome; Financial Interests, Personal, Other: Roche, Pfizer, AstraZeneca; Financial Interests, Personal, Ownership Interest: MEDSIR, Initia-Research. J.M. Pérez García: Financial Interests, Personal, Full or part-time Employment: MEDSIR; Financial Interests, Personal, Advisory Role: Lilly, Roche, Eisai, Daiichi Sankyo, AstraZeneca, Seattle Genetics, Gilead; Financial Interests, Personal, Other: Roche. P. Tolosa Ortega: Financial Interests, Personal, Invited Speaker: Novartis, Pfizer, Lilly, Seagen, AstraZeneca, Daiichi Sankyo and MSD; Financial Interests, Personal, Advisory Board: Novartis, Adamed, Seagen and Daiichi Sankyo; Financial Interests, Personal, Full or part-time Employment, Medical Advisor and Madical Monitor: SOLTI; Financial Interests, Institutional, Funding: Novartis. A. Fernandez Ortega: Financial Interests, Personal, Other: Novartis. I. Blancas López-Barajas: Financial Interests, Personal, Advisory Board: AstraZeneca, Bristol Myers Squibb, Celgene, Daiichi Sankyo, Eisai, Gilead, Grünenthal, GSK, Lilly, MSD, Novartis, Pfizer, Pierre-Fabre, Roche, Seagen; Financial Interests, Personal, Full or part-time Employment: Medical Scientia Innovation Research; Financial Interests, Institutional, Funding: AstraZeneca, Lilly, Roche, Agendia; Financial Interests, Institutional, Research Grant: Pfizer; Other, Support for attending meetings and/or travel: AstraZeneca, Bristol Myers Squibb, Daiichi Sankyo, Gilead, Lilly, Novartis, Pfizer, Roche, Pierre Fabre. C. Saura Manich: Financial Interests, Personal, Advisory Board: AstraZeneca, Daiichi Sankyo, Eisai, Exact Sciences, Exeter Pharma, F. Hoffmann - La Roche Ltd., Gilead, Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Philips, Pierre Fabre, PintPharma, Puma, Roche Farma, Sanofi Avenits, Seagen, Zymeworks, Pharmalex Spain SLU; Financial Interests, Personal, Expert Testimony: Boehringer Ingelheim, Bristol Meyers Squibb, Genentech, Innoup, Millenium; Financial Interests, Personal, Other, SC: Byondis B.V., GSK, Macrogenics, Menarini, Merus, Synthon Biopharpaceuticals; Financial Interests, Institutional, Research Grant: AstraZeneca, Bayer Pharma, Boehringer Ingelheim, Bristol Myers Squibb (BMS), Cytomx Therapeutics, Daiichi Sankyo, Eli Lilly and Company, F. Hoffmann-La Roche Ltd., Genentech, GSK, Immunomedics, Innoup Farma, Macrogenics, Menarini Ricerche, Merus, Novartis, Pfizer, Puma, Roche, Sanofi-Aventis, Seattle Genetics; Financial Interests, Institutional, Invited Speaker: Byondis B.V.; Non-Financial Interests, Member: Spanish Society of Medical Oncology (SEOM), American Society for Clinical Oncology (ASCO), Geicam (Spanish Breast Cancer Research Group), European Society for Medical Oncology (ESMO), Sinology Society of the Official College of Physicians of Barcelona (COMB); Non-Financial Interests, Member, Junta Directiva y Comité Científico: SOLTI group (Academic research group in breast cancer). E.M. Ciruelos: Financial Interests, Personal, Other, Speakers Bureau. Educational activities: Roche; Financial Interests, Personal, Invited Speaker, Symposia and Educational activities: Roche; Financial Interests, Personal, Advisory Board, Non-permanent advisor: Roche, Lilly, Novartis, Pfizer, Daiichi Sankyo, MSD; Financial Interests, Personal, Invited Speaker, Symposia and Education: Lilly; Financial Interests, Personal, Invited Speaker, Educational activities: Pfizer; Financial Interests, Personal, Advisory Board, Non-permanent advisor, Travel accommodation: AstraZeneca; Financial Interests, Personal, Other, Advisory Board: Gilead; Financial Interests, Personal, Other, Advisory Board, Invited speaker: Seagen; Financial Interests, Institutional, Funding, PI for Patricia 2 trial (sponsor: SOLTI Group): Pfizer; Financial Interests, Institutional, Funding, PI for Prometeo 2 trial (sponsor: SOLTI Group): Pfizer; Financial Interests, Institutional, Funding, PI for TATEN trial (sponsor: SOLTI Group): MSD; Financial Interests, Institutional, Funding, PI for ATREZZO trial (sponsor: SOLTI Group): Roche; Non-Financial Interests, Member of Board of Directors, Non-profit organization dedicated to breast cancer research: SOLTI Cooperative Group; Non-Financial Interests, Advisory Role, Scientific Evaluator at ISCIII (Spanish Government Academic Research Platform): Instituto de Salud Carlos III. F. Gómez-Peralta: Financial Interests, Personal, Funding: Lilly; Financial Interests, Personal, Research Grant: Abbot Diabetes; Financial Interests, Personal, Speaker’s Bureau: Eli Lilly, Abbot Diabetes, Novartis, Sanofi, Novo Nordisk, Boehringer Ingelheim, AstraZeneca, Bristol Myers Squibb. S.V. García Vicente, C. Jiménez-Cortegana, J. Rodríguez Morató, L. Mina, M. Sampayo Cordero: Financial Interests, Personal, Full or part-time Employment: MEDSIR. J. Cortés: Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, Seattle Genetics, Daiichi Sankyo, Lilly, MSD, LEUKO, Bioasis, Clovis oncology, Boehringer Ingelheim, Ellipses, Hibercell, BioInvent, Gemoab, Gilead, Menarini, Zymeworks, Reveal Genomics, Jazz Pharmaceuticals, AbbVie, Scorpion Therapeutics, Biocon; Financial Interests, Personal, Invited Speaker: Roche, Novartis, Eisai, Pfizer, Lilly, MSD, Daiichi Sankyo; Financial Interests, Personal, Other, Consulting/advisor: Expres2ion Biotechnologies; Financial Interests, Personal, Other, consulting: Bridgebio; Financial Interests, Personal, Stocks/Shares: MAJ3 Capital; Financial Interests, Personal, Stocks/Shares, (relative): Leuko; Financial Interests, Institutional, Research Grant: Roche, Ariad Pharmaceuticals, AstraZeneca, Baxalta GMBH/Servier Affaires, Bayer healthcare, Eisai, Guardant health, MSD, Pfizer, Piqur Therapeutics, Queen Mary University of London; Other, Travel cost and expenses: Roche, Novartis, Eisai, Daiichi Sankyo, Pfizer, Gilead, AstraZeneca, Stemline Therapeutics; Other, travel cost and expenses: MSD. All other authors have declared no conflicts of interest.