187O - Capivasertib and fulvestrant for patients (pts) with aromatase inhibitor (AI)-resistant HR+/HER2- advanced breast cancer (ABC): subgroup analyses from the Phase 3 CAPItello-291 trial

Background

Capivasertib is a potent, selective pan-AKT inhibitor. In the phase III CAPItello-291 trial in pts with AI-resistant, HR+/HER2– ABC, the addition of capivasertib to fulvestrant (fulv) significantly improved the dual primary endpoints of PFS in the overall (hazard ratio [HR] 0.60; 95% confidence interval [CI] 0.51–0.71; p<0.001) and AKT pathway-altered population (HR 0.50; 95% CI 0.38–0.65; p<0.001) compared with placebo plus fulv. Here we report PFS in key clinically relevant subgroups (data cut-off Aug 15, 2022).

Methods

Pts were randomised 1:1 to receive fulv (500 mg IM on days 1 and 15 of cycle 1, and day 1 of each subsequent 28-day cycle) with either placebo or capivasertib (400 mg twice daily; 4 days on, 3 days off). Randomisation was stratified by the presence of liver metastases, prior use of CDK4/6 inhibitor (CDK4/6i) and region. Preplanned exploratory PFS analyses included prior use of CDK4/6i, prior chemotherapy (CT) for ABC, and presence of liver metastases.

Results

Overall, 708 pts were randomised to capivasertib-fulv (n=355) or placebo-fulv (n=353): 289 pts (40.8%) had AKT pathway-altered tumours; 496 pts (70.1%) had received prior CDK4/6i; 129 pts (18.2%) had received prior CT for ABC, and 306 pts (43.2%) had liver metastases. PFS benefit of capivasertib-fulv over placebo-fulv was broadly consistent across key clinical subgroups (Table). In cross-subgroup comparison, placebo-fulv efficacy was lower in pts with prior CDK4/6i exposure and pts with liver metastases. Findings in the AKT pathway-altered population were consistent with the overall population and will be presented. Table: 187O

PFS in the overall population

Conclusions

Exploratory PFS analyses confirmed a consistent benefit of treatment with capivasertib-fulv vs fulv alone in clinically relevant subgroups, including pts with prior CDK4/6i exposure or liver metastases, subgroups with poor prognosis on fulv alone.

Clinical trial identification

NCT04305496, Actual Primary Completion Date: August 15, 202.2 Estimated Study Completion Date: June 7, 2024.

Editorial acknowledgement

AstraZeneca-funded medical writing support was provided by Suzanne Patel, Ph.D., from BOLDSCIENCE Inc. Capivasertib was discovered by AstraZeneca subsequent to a collaboration with Astex Therapeutics (and its collaboration with the Institute of Cancer Research and Cancer Research Technology Limited).

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

M. Oliveira: Financial Interests, Personal, Advisory Board: AstraZeneca, Daiichi Sankyo / AstraZeneca, GSK, Gilead, PUMA Biotechnology, Pierre Fabre, Roche, Seagen, iTEOS, MSD; Financial Interests, Personal, Invited Speaker: Eisai, Gilead, Guardant Health, MSD, Novartis, Pfizer, Pierre Fabre, Roche, Seattle Genetics, AstraZeneca; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Boehringer-Ingelheim, GSK, Genentech, Immunomedics, Novartis, Roche, Seattle Genetics, Zenith Epigenetics, Gilead; Financial Interests, Invited Speaker: Roche; Non-Financial Interests, Invited Speaker: SOLTI Breast Cancer Research; Other, Travel Grant: Pierre Fabre, Roche, Novartis, Eisai. H.S. Rugo: Financial Interests, Personal, Advisory Role: Napo Pharmaceuticals, Scorpion Therapeutics, Blueprint Medicines, Puma Biotechnology; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Merck, AstraZeneca, Gilead Sciences; Financial Interests, Institutional, Funding: OBI Pharma, Pfizer, Novartis, Lilly, Genentech, Merck, Daiichi Sankyo, Sermonix Pharmaceuticals, AstraZeneca, Gilead Sciences, Astellas Pharma, Pionyr, Taiho Oncology, Veru; Financial Interests, Institutional, Invited Speaker: GlaxoSmithKline. S.J. Howell: Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Speaker’s Bureau: Pfizer; Financial Interests, Personal, Advisory Board: Pfizer. F. Dalenc: Non-Financial Interests, Institutional, Advisory Role: AstraZeneca, Daiichi, Pfizer, Seagen, Gilead, Novartis. J. Cortés: Financial Interests, Personal, Advisory Board: Roche, Celgene, Cellestia, AstraZeneca, Seattle Genetics, Daiichi Sankyo, Erytech, Athenex, Polyphor, Lilly, MERCK SHARP& DOHME, GSK, LEUKO, Bioasis, Clovis oncology, Boehringer Ingelheim, Ellipses, Hibercell, BioInvent, Gemoab, Gilead, Menarini, Zymeworks, Reveal Genomics; Financial Interests, Personal, Invited Speaker: Roche, Novartis, Celgene, Eisai, Pfizer, Samsung Bioepis, Lilly, MERCK SHARP& DOHME, Daiichi Sankyo; Financial Interests, Personal, Other, Consulting/advisor: Expres2ion Biotechnologies; Financial Interests, Personal, Stocks/Shares: MedSIR, Nektar Therapeutics; Financial Interests, Institutional, Research Grant: Roche, Ariad Pharmaceuticals, AstraZeneca, Baxalta GMBH/Servier Affaires, Bayer healthcare, Eisai, Guardanth health, Merck Sharp&Dohme, Pfizer, Piqur Therapeutics, Puma B, Queen Mary University of London; Other, Travel cost and expenses: Roche, Novartis, Eisai, Daiichi Sankyo, Pfizer, Gilead, AstraZeneca. H.L. Gomez Moreno: Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Roche, Novartis, AstraZeneca, Bristol Myers Squibb, Lilly; Financial Interests, Personal, Funding: MSD Oncology. X. Hu: Financial Interests, Personal, Invited Speaker: AstraZeneca, Roche, Novartis, Pfizer. K. Jhaveri: Financial Interests, Personal, Advisory Board: Novartis, AstraZeneca, Pfizer, Genentech/Roche, Lilly/Loxo Oncology, BMS, Scorpion Therapeutics, Biotheranostics, Blueprint Medicines, Taiho Oncology, Jounce Therapeutics, Seattle Genetics, Daiichi Sankyo, AbbVie, Olema, Pharmaceuticals, Sun Pharma Advanced, Research Company Ltd., Menarini/Stemline, Eisai; Financial Interests, Institutional, Funding: Novartis, AstraZeneca, Pfizer, Genentech/Roche, Lilly/Loxo Oncology, Merck, PUMA Biotechnology, Zymeworks, Gilead, Context Therapeutics. S. Loibl: Financial Interests, Institutional, Advisory Board, Member: Amgen, AstraZeneca, BMS, Celgene, EirGenix, GSK, Lilly, Pierre Fabre, Roche, Seagen, AbbVie, Sanofi, Gilead, Merck, Novartis, Relay Therapeutics; Financial Interests, Institutional, Invited Speaker: AstraZeneca, DSI, Novartis, Pfizer, Roche, Gilead, Seagen; Financial Interests, Institutional, Advisory Board: DSI, Pfizer, Olema; Financial Interests, Personal, Invited Speaker: Medscape; Financial Interests, Personal, Full or part-time Employment, CEO: GBG Forschungs GmbH; Financial Interests, Institutional, Invited Speaker, Ki67: VM Scope GmbH; Financial Interests, Institutional, Research Grant: AstraZeneca, Celgene, Novartis, Immunomedics/Gilead, Pfizer, Roche, Daiichi Sankyo; Financial Interests, Institutional, Funding: AbbVie, Molecular Health; Financial Interests, Personal, Other, PIPenelope/Padma: Pfizer; Financial Interests, Personal, Other, SC PALOMA3: Pfizer; Financial Interests, Personal, Other, SC SOLAR1: Novartis; Financial Interests, Personal, Other, SC ASCENT: Immunomedics/Gilead; Financial Interests, Personal, Other, SC HERCLIMB: Seagen; Financial Interests, Personal, Other, SC Katherine: Roche; Financial Interests, Personal, Other, SC Capitello; EC Cambria 1: AstraZeneca; Financial Interests, Personal, Other, SC Inavo: Roche; Financial Interests, Personal, Other, SC Destiny B05; SC Destiny B09: Daiichi Sankyo; Non-Financial Interests, Principal Investigator, After publication of primary endpoint: PI Aphinity; Non-Financial Interests, Advisory Role, Group in Germany responsible for breast cancer guidelines: AGO Kommission Mamma; Non-Financial Interests, Member, German Gynaecological Oncology society: AGO; Non-Financial Interests, Member, German Cancer Society: DKG; Non-Financial Interests, Member: ASCO; Non-Financial Interests, Member, Member guideline committee; past chair in ESMO Breast: ESMO; Other, EP14153692.0No financial interest, Institutional: Patent; Other, EP21152186.9No financial interest, institutional: Patent; Other, EP15702464.7No financial interest, institutional: Patent; Other, EP19808852.8 No financial interest, Institutional: Patent. Y.H. Park: Financial Interests, Personal and Institutional, Writing Engagements: Novartis, Pfizer, Merck, Roche, Lilly, AstraZeneca, Daiichi Sankyo; Financial Interests, Personal and Institutional, Advisory Board: Novartis, Pfizer, Merck, Roche, Lilly, AstraZeneca , Daiichi Sankyo, Gilead Sciences, Boryung; Financial Interests, Personal and Institutional, Principal Investigator: Novartis, Pfizer, Merck, Roche, Lilly, AstraZeneca, Daiichi Sankyo, Gilead Sciences, Boryung; Non-Financial Interests, Personal and Institutional, Writing Engagements: Novartis, Pfizer, Merck, Roche, Lilly, AstraZeneca, Daiichi Sankyo; Non-Financial Interests, Personal and Institutional, Advisory Board: Novartis, Pfizer, Merck, Roche, Lilly, AstraZeneca, Daiichi Sankyo; Non-Financial Interests, Personal and Institutional, Principal Investigator: Novartis, Pfizer, Merck, Roche, Lilly, AstraZeneca, Daiichi Sankyo; Financial Interests, Personal and Institutional, Invited Speaker: Pfizer, Merck, Roche, Lilly, AstraZeneca, Daiichi Sankyo; Financial Interests, Personal and Institutional, Research Grant: Pfizer, Roche, Lilly, AstraZeneca; Non-Financial Interests, Personal and Institutional, Invited Speaker: Pfizer, Merck, Roche, Lilly, AstraZeneca, Daiichi Sankyo; Non-Financial Interests, Personal and Institutional, Research Grant: Pfizer, Merck, Roche, Lilly, AstraZeneca; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Advisory Board: Eisai, Menarini; Financial Interests, Personal, Principal Investigator: Menarini; Financial Interests, Institutional, Research Grant: Gencurix, Genome Insight, NGenbio; Financial Interests, Institutional, Principal Investigator: Gencurix. J. Sohn: Financial Interests, Personal, Stocks/Shares, Immediate Family Member: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: MSD, Roche, Novartis, AstraZeneca, Lilly, Pfizer, GSK, Daiichi Sankyo, Sanofi, Boehringer Ingelheim, Seagen. E. Tokunaga: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Eli Lilly, Daiichi Sankyo. L. Zhukova: Financial Interests, Personal and Institutional, Principal Investigator: AstraZeneca, Novartis, Biocad. I. Wadsworth: Financial Interests, Personal and Institutional, Other, Paid employee for Phastar and contracted to work full time for AstraZeneca as a statistician.: AstraZeneca. G. Schiavon: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. A. Foxley: Financial Interests, Personal, Full or part-time Employment, Employee: AstraZeneca; Financial Interests, Personal, Stocks/Shares, Stock as part of remuneration for employment: AstraZeneca. N. Turner: Financial Interests, Personal, Advisory Role: Novartis, AstraZeneca, Pfizer, Bristol Myers Squibb, Merck Sharp & Dohme, Lilly, Repare Therapeutics, Zeno pharmaceuticals, Roche, Inivata; Financial Interests, Institutional, Funding: Pfizer, Roche, AstraZeneca, Clovis Oncology, Bio-Rad, Guardant Health, Inivata, InVitae, Personalis, Natera. All other authors have declared no conflicts of interest.