183MO - Capivasertib and fulvestrant (F) for patients (pts) with aromatase inhibitor (AI)-resistant HR+/HER2- advanced breast cancer (ABC): Second progression-free survival (PFS2) and time to first subsequent chemotherapy (TFSC) in the CAPItello-291 trial

Background

In the phase III CAPItello-291 trial, the addition of capivasertib (a potent, selective pan-AKT inhibitor) to F in pts with AI-resistant, HR+/HER2– ABC, significantly improved PFS compared with placebo + F (hazard ratio [HR] 0.60; 95% confidence interval [CI] 0.51–0.71; p<0.001), including in patients with PIK3CA/AKT1/PTEN-altered tumours (HR 0.50; 95% CI 0.38–0.65; p<0.001). We report outcomes after study therapy (data cut-off 15 Aug 2022).

Methods

Details of subsequent anti-cancer treatments were recorded after the progression of disease on study therapy (PFS). PFS2 was a secondary endpoint, defined as the time from randomisation to second progression (i.e. the earliest of either death or a progression event following treatment start after first progression). Time from randomisation to the start of subsequent chemotherapy (TFSC; defined as the first of death or chemotherapy treatment start) was an exploratory endpoint.

Results

708 pts were randomised to capivasertib + F (n=355) or placebo + F (n=353): 289 pts (40.8%) had PIK3CA/AKT1/PTEN-altered tumours (289/602, 48.0% of pts with known tumour sequencing results). At the time of this analysis, 238 (67.0%) pts in the capivasertib + F arm and 264 (74.8%) pts in the placebo + F arm had received subsequent anti-cancer therapy; most commonly cytotoxic chemotherapy (56.1% vs 61.2%), hormonal therapy (27.6% vs 30.3%) and targeted therapy (18.9% vs 25.8%). PFS2 and TFSC favoured capivasertib + F over placebo + F in the overall and PIK3CA/AKT1/PTEN-altered populations (Table). Table: 183MO

Conclusions

Subsequent treatments were similar between arms, and the benefit of capivasertib + F was retained through PFS2. In addition, capivasertib + F also resulted in a clinically meaningful delay in the initiation of chemotherapy compared to F alone.

Clinical trial identification

NCT04305496.

Editorial acknowledgement

AstraZeneca-funded medical writing support was provided by Suzanne Patel, PhD, 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

H.S. Rugo: Financial Interests, Personal, Other, Consultancy/advisory support: NAPO, Mylan/Viatris, Daiichi Sankyo, Eisai; Financial Interests, Institutional, Invited Speaker: Novartis, Lilly, Pfizer, OBI Pharma, F. Hoffmann-La Roche AG/Genentech, Inc., Daiichi, AstraZeneca, Gilead Sciences, Inc., Merck; Financial Interests, Institutional, Research Grant: Stemline Therapeutics, Ambryx; Non-Financial Interests, Advisory Role, I advise a number of companies without compensation: various. M. Oliveira: Financial Interests, Personal, Advisory Board: AstraZeneca, Daiichi Sankyo / AstraZeneca, Gilead, Lilly, MSD, Relay Therapeutics, Roche, Seagen, Cureo Science, iOne, Pfizer; Financial Interests, Personal, Invited Speaker: Eisai, Gilead, Pfizer, Roche, Seagen, AstraZeneca, Lilly, Medscape, AstraZeneca, AstraZeneca; Financial Interests, Personal, Other, Educational activity: Libbs; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Boehringer-Ingelheim, GSK, Roche, Seattle Genetics, Zenith Epigenetics, Gilead, Ayala Pharmaceuticals, Pfizer; Financial Interests, Invited Speaker: Roche; Non-Financial Interests, Member of Board of Directors, Head: SOLTI Breast Cancer Research; Other, Travel Grant: Pierre Fabre, Eisai, Gilead, AstraZeneca. S.J. Howell: Financial Interests, Institutional, Sponsor/Funding, Study sponsor. Per patient payments to institution: AstraZeneca; Financial Interests, Institutional, Research Grant: Eli Lilly UK; Financial Interests, Personal, Other, Consulting fees: Pfizer; Financial Interests, Personal, Other, Payment or honoraria for lectures, presentations, speakers bureaus, abstract writing or educational events: Eli Lilly UK, Pfizer Ltd., Novartis, AstraZeneca; Financial Interests, Personal, Other, Travel and accommodation: Novartis; Financial Interests, Personal, Advisory Board, Participation on a Data Safety Monitoring Board or Advisory Board: Eli Lilly UK; Non-Financial Interests, Institutional, Other, Medical writing support (no payments): BOLDSCIENCE. F. Dalenc: Financial Interests, Institutional, Other, Honoraria: Lilly, Gilead, AstraZeneca; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Daiichi Sankyo, Novartis, Gilead, Pfizer. 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. H.L. Gomez Moreno: Financial Interests, Personal, Invited Speaker: Roche, BMS, MSD, Novartis, Pfizer, Exact Sciences, Tecnofarma, AstraZeneca, Roche, MSD, AstraZeneca. S. Loibl: Financial Interests, Institutional, Advisory Board, Member: Amgen, AstraZeneca, BMS, Celgene, DSI, 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, Stemline-Menarini; Financial Interests, Institutional, Advisory Board: 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 Quantifier: VMscope GmbH; Financial Interests, Institutional, Research Grant: AstraZeneca, Celgene, Novartis, Immunomedics/Gilead, Pfizer, Roche, Daiichi Sankyo; Financial Interests, Institutional, Funding: AbbVie, Molecular Health, Greenwich Life Sciences; 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, EP19808852.8 No financial interest, Institutional: Patent. Y.H. Park: Financial Interests, Personal, Advisory Board: AstraZeneca, Pfizer, Roche, Novartis, MSD, Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: AstraZeneca, Pfizer, Roche, Novartis, MSD, Daiichi Sankyo; Financial Interests, Institutional, Other, Research Grant: AstraZeneca, Pfizer, Roche, MSD; Financial Interests, Institutional, Invited Speaker: Pfizer; Non-Financial Interests, Principal Investigator: AstraZeneca, Pfizer, Novartis, MSD, Lilly, Roche, Daiichi Sankyo. M. Toi: Financial Interests, Personal, Invited Speaker: AstraZeneca, Chugai, Devicore medical Japan, Eisai, Exact Science, MSD, Nippon-Kayaku, Novartis, Pfizer, Shimadzu, Sysmex, Taiho, Takeda, Yakult; Financial Interests, Personal, Advisory Board, This company is not working any more: Athenex Oncology; Financial Interests, Personal, Advisory Board: BMS, Bertis, Kansai Medical Net, Terumo; Financial Interests, Personal, Advisory Board, + Invited speaker: Daiichi Sankyo, Eli Lilly and companies; Financial Interests, Personal, Invited Speaker, + Invited speaker: Kyowa-Kirin; Financial Interests, Institutional, Research Grant, Research grant to a basic study: AFI technology, Astellas, Luxonus, Sanwa Shurui; Financial Interests, Institutional, Research Grant, Research grant to a basic-cliical studySteering committee member (non-financial interest): AstraZeneca; Financial Interests, Institutional, Research Grant, Research Grant to Institution, Funding to InstitutionCoordianting PI (non-finacial interest), Steering Committee member (non-financial interest), Local PI (non-finacial interest): Chugai; Financial Interests, Institutional, Research Grant, Research grant to a preclinical study Steering committee member (non-financial interest): Daiichi Sankyo; Financial Interests, Institutional, Funding, Funding to a clinical studyCoordinating PI of a neoadjuvant study (non-financial interest): Eisai; Financial Interests, Institutional, Funding, Funding to a clinical studySteering committee member (non-financial interest): Eli Lilly and companies; Financial Interests, Institutional, Research Grant, Research grant to a clinical study: GL Science, Yakult; Financial Interests, Institutional, Research Grant, Research grant to a basic-clinical study: Nippon-Kayaku; Financial Interests, Institutional, Funding, Research Grant to Institution Coordianting PI (non-finacial interest): Pfizer; Financial Interests, Institutional, Research Grant, Research grant to a basic investigation: Shimadzu; Financial Interests, Institutional, Research Grant, Research grant to clinical study: Takeda; Financial Interests, Institutional, Funding, Funding to translational research of JBCRG assoc. studies: The Japan Breast Cancer Research Group association; Financial Interests, Institutional, Funding, Funding to translational research of KBCRN assoc studies: The Kyoto Breast Cancer Research Network association; Financial Interests, Institutional, Research Grant, Research grant to a study: Kansai medical Net; Non-Financial Interests, Member of Board of Directors, No salary: The Japanese Onco-Cardiology Society, The Kyoto Breast Cancer Research Network association, The Japan Breast Cancer Research group association, Organisation for Oncology and Translational Research; Non-Financial Interests, Leadership Role, No salary: The Japanese Breast cancer Society; Other, Editorial board member: British Journal of Cancer, Asian Journal of Surgery, Asian Journal of Breast Surgery, Translation Breast Cancer Research; Other, Associate editor: Scientific Reports, Breast Cancer Research and Treatment, Cancer Science, Frontiers in Women's Cancer. M. Fulford: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. C. D'Cruz: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. I. Wadsworth: Other, Personal, Full or part-time Employment: AstraZeneca. N. Turner: Financial Interests, Personal, Advisory Board: AstraZeneca, Lilly, Novartis, Pfizer, Roche/Genentech, GSK, Zentalis pharmaceuticals, Repare therapeutics, GSK, Relay therapeutics, Gilead, Inivata, Guardant, Exact Sciences; Financial Interests, Institutional, Funding: AstraZeneca, Pfizer, Roche/Genentech, Merck Sharpe and Dohme, Invitae, Inivata, Personalis, Natera; Financial Interests, Institutional, Other, provision of materials: BioRad; Financial Interests, Institutional, Other, Provision of assays: Guardant Health. All other authors have declared no conflicts of interest.