LBA19 - Capivasertib (C) + paclitaxel (P) as first-line treatment of metastatic triple-negative breast cancer (mTNBC): The CAPItello-290 phase III trial

Background

In the randomised Phase 2 PAKT trial, adding the pan-AKT inhibitor C to first-line P in patients (pts) with mTNBC led to significantly longer progression-free survival (PFS) and favourable overall survival (OS) vs placebo (Pbo) + P. The global CAPItello-290 Phase 3 trial further assessed the efficacy and safety of C+P vs Pbo+P as first-line treatment for mTNBC.

Methods

The study enrolled pts previously untreated for locally advanced or mTNBC; prior (neo)adjuvant chemotherapy within 6 months (12 months for taxanes) of randomisation was not allowed. Pts were randomised 1:1 to P 80 mg/m² (Day 1 of Weeks 1–3 of each 4-week cycle) + C 400 mg or Pbo twice daily (Days 2–5 of Weeks 1–3). PIK3CA/AKT1/PTEN alterations were analysed by retrospective central molecular testing of primary or recurrent tumour sample. The dual primary endpoints were OS in the overall population and in pts with PIK3CA/AKT1/PTEN-altered tumours.

Results

From Jul 2019–Feb 2022, 812 pts were randomised. At baseline, 70.0% had visceral metastases and 50.0% had received prior (neo)adjuvant chemotherapy. PIK3CA/AKT1/PTEN tumour alterations were detected in 30.7% of pts. The primary endpoints of OS in the overall population and in pts with PIK3CA/AKT1/PTEN-altered tumours were not met (data cutoff [DCO] 18 Mar 2024; Table). The secondary endpoint of PFS numerically favoured C+P over Pbo+P (DCO 25 May 2022; Table). The most common adverse events (AEs) with C+P were diarrhoea (76.4% vs 26.0% with Pbo+P) and anaemia (39.3% vs 30.7%). The most common Grade ≥3 AEs with C+P were diarrhoea (12.7% vs 0.7%) and neutropenia (7.2% vs 6.6%). Discontinuation of C/Pbo due to AEs occurred in 8.5%/4.9% pts. Table: LBA19

HR calculated by Cox proportional hazards model stratified by (yes/no): PIK3CA/AKT1/PTEN-altered (overall population only), visceral metastases, prior (neo)adjuvant chemotherapy. CI, confidence interval; HR, hazard ratio.

Conclusions

First-line C+P for mTNBC did not meet the predefined threshold for improving OS vs Pbo+P in either the overall population or in pts with PIK3CA/AKT1/PTEN-altered tumours. PFS numerically favoured C+P vs Pbo+P. The safety profile of C+P was broadly consistent with the known profiles of C and P.

Clinical trial identification

NCT03997123.

Editorial acknowledgement

AstraZeneca-funded medical writing support was provided by Stavroula Bitsi, PhD, of BOLDSCIENCE Inc. Capivasertib was discovered by AstraZeneca after a collaboration with Astex Therapeutics (and its partnership with the Institute of Cancer Research and Cancer Research Technology Limited).

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

P. Schmid: Financial Interests, Personal, Advisory Board: AstraZeneca, Novartis, Pfizer, Roche, Gilead, Eisai, MSD, Seagen, Lilly; Financial Interests, Institutional, Research Grant: AstraZeneca, Genentech, Roche. H.L. McArthur: Financial Interests, Personal, Advisory Board: Lilly, Pfizer, Immunomedics, Merck, Seattle Genetics, Daiichi Sankyo, Bristol Myers Squibb, AstraZeneca, Puma Biotechnology, Gilead, Crown Bioscience, Roche, Novartis, Genentech; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb, MedImmune, AstraZeneca, Merck. J. Cortés: Financial Interests, Personal, Advisory Board, Consulting fees: Roche, AstraZeneca, Seattle Genetics, Daiichi Sankyo, Lilly, MSD, Leuko, Bioasis, Clovis Oncology, Boehringer Ingelheim, Ellipses, Hibercell, BioInvent, Gemoab, Gilead, Menarini, Zymeworks, Reveal Genomics, Scorpion Therapeutics, Expres2ion Biotechnologies, Jazz Pharmaceuticals, AbbVie, BridgeBio, Biontech, Biocon, Circle Pharma; Financial Interests, Personal, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Roche, Novartis, Eisai, Pfizer, Lilly, MSD, Daiichi Sankyo, AstraZeneca, Gilead, Steamline Therapeutics; Financial Interests, Personal, Other, Support for attending meetings and/or travel: Roche, Novartis, Eisai, Pfizer, Daiichi Sankyo, AstraZeneca, Gilead, MSD, Steamline Therapeutics; Financial Interests, Personal, Stocks/Shares: MAJ3 Capital; Financial Interests, Personal, Stocks/Shares, (relative): Leuko; Financial Interests, Institutional, Research Funding: Roche, Ariad pharmaceuticals, AstraZeneca, Baxalta GMBH/Servier Affaires, Bayer healthcare, Eisai, F.Hoffman-La Roche, Guardant health, MSD, Pfizer, Piqur Therapeutics, Iqvia, Queen Mary University of London. B. Xu: Financial Interests, Personal, Speaker, Consultant, Advisor, Consulting fees: AstraZeneca, Novartis. F. Cardoso: Financial Interests, Personal, Other, Consultancy: Amgen, Astellas/Medivation, AstraZeneca, Celgene, Daiichi Sankyo, Eisai, GE Oncology, Genentech, GSK, Macrogenics, Medscape, Merck-Sharp, Merus BV, Mylan, Mundipharma, Novartis, Pfizer, Pierre-Fabre, Prime Oncology, Roche, Sanofi, Samsung Bioepis, Seagen, Teva; Financial Interests, Personal, Advisory Board: Gilead, Iqvia, Touchime; Financial Interests, Institutional, Local PI: Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Bayer, Daiichi, Eisai, Fresenius GmbH, Genentech, GSK, Ipsen, Incyte, Nektar Therapeutics, Nerviano, Novartis, Macrogenics, Medigene, MedImmune, Merck, Millenium, Pfizer, Pierre-Fabre, Roche, Sanofi-Aventis, Sonus, Taiho Oncology, Tesaro, Tigris, Wilex, Wyeth, Gilead; Non-Financial Interests, Leadership Role, President: ABC Global Alliance and ABC Consensus Conference and Guidelines; Non-Financial Interests, Member: ESMO, ESO, EORTC, BCG, IBCSG, SOLTI, ASCO, AACR, EACR, SIS, ASPIC. M.L. Casalnuovo: Financial Interests, Personal, Speaker, Consultant, Advisor, Consulting or Advisory Role: AstraZeneca, Janssen Oncology. R. Freitas Jr: Financial Interests, Institutional, Other, All support for the present manuscript (e.g., funding, provision of study materials, medical writing, article processing charges, etc.): Roche; Financial Interests, Institutional, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Novartis, AstraZeneca, Daiichi Sankyo; Financial Interests, Institutional, Advisory Board, Participation on a Data Safety Monitoring Board or Advisory Board: Novartis; Financial Interests, Personal, Other, Support for attending meetings and/or travel: Libbs, MSD, Blanver. H. Iwata: Financial Interests, Personal, Advisory Board: Chugai, Daiichi Sankyo, AstraZeneca, Lilly, Sanofi; Financial Interests, Personal, Invited Speaker: Chugai, Daiichi Sankyo, AstraZeneca, Lilly, Pfizer, Sanofi, Taiho; Financial Interests, Personal and Institutional, Steering Committee Member: Chugai, Daiichi Sankyo, AstraZeneca, MSD, Amgen, Sanofi, Novartis, Pfizer, Kyowa Hakko Kirin; Financial Interests, Personal and Institutional, Local PI: Lilly, Bayer, Behringer, Nihon Kayaku. M.E. Robson: Financial Interests, Personal, Other, Review guideline pathways: Change Healthcare; Financial Interests, Personal, Invited Speaker, Speaker at CME events (NOT speaker's bureau): Physician's Education Resource, MJH Holdings; Financial Interests, Personal, Advisory Board, Speaker at CME events (NOT speaker's bureau): MyMedEd; Financial Interests, Personal, Invited Speaker, Speaker at CME events (not Speakers' bureau): Clinical care Options; Financial Interests, Institutional, Local PI, Funding for research study (ICEBERG, dating to 2007): AstraZeneca; Financial Interests, Personal, Steering Committee Member, Steering Committee Member for CAPITELLO-290, uncompensated: AstraZeneca; Financial Interests, Institutional, Other, Co-PI for Merck IIT of neoadjuvant olaparib/pembrolizumab in BRCA carriers, no personal compensation: Merck; Financial Interests, Personal, Steering Committee Member, Steering Committee member for KEYLNK-009, no compensation: Merck; Financial Interests, Institutional, Local PI, Local PI of KEYLNK009: Merck; Financial Interests, Institutional, Other, Local co-PI of clinical trial of ZEN03694 and talazoparib in TNBC, no personal compensation: Pfizer; Financial Interests, Institutional, Local PI, Local PI of clinical trial: Artios Pharma; Non-Financial Interests, Advisory Role: Zenith Pharmaceuticals, Tempus Labs; Non-Financial Interests, Advisory Role, Uncompensated advisor: Foundation Medicine; Non-Financial Interests, Personal, Other, Editorial services for medical writing of reports resulting from OlympiAD trial: AstraZeneca; Non-Financial Interests, Personal, Other, Editorial services for write-ups of trials: Merck; Non-Financial Interests, Member: ASCO. R. Villalobos Valencia: Financial Interests, Personal, Invited Speaker: AstraZeneca, Sthendal; Financial Interests, Personal, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Novartis, Pfizer, Eli Lilly; Financial Interests, Personal, Expert Testimony: AstraZeneca, Gilead; Financial Interests, Personal, Other, Meeting travel: AstraZeneca, Gilead, Roche, Asofarma, Janssen; Financial Interests, Personal, Advisory Board: AstraZeneca, Gilead; Non-Financial Interests, Personal, Member: ASCO, ESMO. A. Lloyd: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks or ownership: AstraZeneca. C. D'Cruz: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks or ownership: AstraZeneca. A. Foxley: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks or ownership: AstraZeneca. Y.H. Park: Financial Interests, Institutional, Research Grant: MSD, Pfizer, AstraZeneca, Inocras, Gencurix, Roche, Novartis; Financial Interests, Personal, Speaker, Consultant, Advisor, Consulting fees: AstraZeneca, Pfizer, Eli Lilly, Gilead, Menarini, Novartis, MSD, Eisai, Roche, Daiichi Sankyo, Everest; Financial Interests, Institutional, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: AstraZeneca, Pfizer, Eli Lilly, Novartis, Helsinn, MSD, Roche, Daiichi Sankyo, Gilead; Financial Interests, Personal, Other, Support for attending meetings and/or travel: Gilead, AstraZeneca, Pfizer; Financial Interests, Personal, Advisory Board, Participation on a Data Safety Monitoring Board or Advisory Board: AstraZeneca, Menarini, Roche, Pfizer, Novartis, Daiichi Sankyo; Non-Financial Interests, Personal, Non financial benefits, Receipt of equipment, materials, drugs, medical writing, gifts or other services: AstraZeneca, Pfizer, MSD, Roche, Daewong, Dong-A ST, Sanofi. All other authors have declared no conflicts of interest.