LBA18 POSEIDON randomized phase II trial: Tamoxifen (TAM) + taselisib or placebo (PLA) in patients (pts) with hormone receptor positive (HR+)/HER2- metastatic breast cancer (MBC)

ABSTRACT

Background: Taselisib is an oral inhibitor of class I α, δ, and ϒ isoforms of PI3K that has demonstrated clinical activity in combination with TAM (Baird R et al, CCR 2019). Methods: POSEIDON is an international, multicenter, randomized (11) phase II trial of TAM + taselisib or PLA in pts with HR+/HER2- MBC after prior endocrine treatment (ET). Cross-over was allowed. Primary endpoint unstratified progression-free survival (PFS;local assessment). Secondary endpoints safety, RECIST 1.1 overall response rate (ORR;complete response [CR] + partial response [PR]), clinical benefit rate (CBR;CR + PR + stable disease >6 months) and overall survival (OS). 180 pts were required to detect a PFS constant hazard ratio (HR) of 0.64 (ß=90%, 2-sided α=0.2). Accrual closed prematurely due to Covid-19, decreasing the power to 83%. Results: 152 pts (median age 63) enrolled (Table), median follow-up 26.4 months (m). Addition of taselisib to TAM increased median PFS from 3.2 to 4.8m (unstratified HR 0.62, 95%CI 0.43-0.93, p=0.02;stratified HR 0.68, 95%CI 0.4-1.2, p=0.16), independently of PIK3CA status. In taselisib arm, ORR 11.8% (95%CI 5.6- 21.3) and CBR 22.4% (95%CI 13.6-33.4);in PLA arm, ORR 2.6% (95%CI 0.3- 9.2) and CBR 14.5% (95%CI 7.5-24.4). Reasons for stopping taselisib / PLA toxicity 22% / 4%, progressive disease 55% / 67%, other (mainly Covid-19) 23% / 29%. Common adverse events (AEs) in taselisib arm diarrhea (36%), nausea (35%), hyperglycemia (28%). Common AEs in PLA arm nausea (21%), fatigue (16%). G3-5 AEs were more common with taselisib (44% vs 5%, p<0.01), mainly diarrhea (11%), hyperglycemia (5%) and transaminitis (5%). OS will be presented. [Formula presented] Conclusions: Addition of taselisib to TAM increased PFS in pts with HR+/HER2-neg MBC but the tolerability of the regimen was poor. Combining ET and PI3K-AKT pathway inhibition using drugs with a better therapeutic index warrants additional study in breast cancer subgroups most likely to benefit. Clinical trial identification EudraCT 2013-003947-51;NCT02301988. Legal entity responsible for the study The Netherlands Cancer Institute (NKI). Funding: POSEIDON is a European investigator-initiated trial, funded by the EU FP7 RATHER consortium (project ID 258967) and EurocanPlatform (project ID 260791), with additional support from an unrestricted research grant from Genentech, and led by the Netherlands Cancer Institute (Amsterdam, the Netherlands), Cambridge Cancer Centre (Cambridge, UK), and Vall d’Hebron Institute of Oncology (Barcelona, Spain). Disclosure M. Oliveira Financial Interests, Personal, Advisory Board Roche;Financial Interests, Personal, Advisory Board GSK;Financial Interests, Personal, Advisory Board PUMA Biotechnology;Financial Interests, Personal, Advisory Board AstraZeneca;Financial Interests, Personal, Invited Speaker Roche;Financial Interests, Personal, Invited Speaker Seattle Genetics;Financial Interests, Personal, Invited Speaker Novartis;Financial Interests, Personal, Invited Speaker MSD;Financial Interests, Personal, Invited Speaker Guardant Health;Financial Interests, Personal, Invited Speaker Pfizer;Financial Interests, Institutional, Invited Speaker Roche;Financial Interests, Invited Speaker Roche;Financial Interests, Personal, Invited Speaker AstraZeneca;Financial Interests, Institutional, Invited Speaker AstraZeneca;Financial Interests, Institutional, Invited Speaker Genentech;Financial Interests, Institutional, Invited Speaker Novartis;Financial Interests, Institutional, Invited Speaker Immunomedics;Financial Interests, Institutional, Invited Speaker Seattle Genetics;Financial Interests, Institutional, Invited Speaker GSK;Financial Interests, Institutional, Invited Speaker Boehringer-Ingelheim;Financial Interests, Institutional, Invited Speaker Zenith Epigenetics;Financial Interests, Personal, Invited Speaker AstraZeneca;Non-Financial Interests, Invited Speaker SOLTI Breast Cancer Research. R.D. Baird Financial Interests, Institutional, Other, Honoraria Molecular P rtners;Financial Interests, Institutional, Advisory Role Shionogi;Financial Interests, Institutional, Advisory Role Daiichi Sankyo;Financial Interests, Institutional, Advisory Role Molecular Partners;Financial Interests, Institutional, Advisory Role Roche/Genentech;Financial Interests, Institutional, Advisory Role Novartis;Financial Interests, Institutional, Advisory Role AstraZeneca;Financial Interests, Institutional, Research Grant AstraZeneca;Financial Interests, Institutional, Research Grant Genentech;Financial Interests, Institutional, Research Grant Shionogi;Financial Interests, Institutional, Research Grant Molecular Partners;Financial Interests, Institutional, Research Grant Sanofi;Financial Interests, Institutional, Research Grant Boehringer Ingelheim;Financial Interests, Institutional, Research Grant Roche;Financial Interests, Institutional, Research Grant Biomarin;Financial Interests, Institutional, Research Grant G1 Therapeutics;Financial Interests, Institutional, Research Grant Carrick Therapeutics;Financial Interests, Personal, Other Shionogi;Financial Interests, Personal, Other AstraZeneca;Financial Interests, Personal, Other Molecular Partners;Financial Interests, Personal, Other Daiichi Sankyo. 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C. Mather Financial Interests, Full or part-time Employment, Immediate family member Clovis Oncology;Financial Interests, Stocks/Shares, Immediate family member Clovis Oncology. J. 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Linn Financial Interests, Personal, Advisory Board Cergentis;Financial Interests, Personal, Advisory Board IBM;Financial Interests, Institutional, Research Grant Agendia;Financial Interests, Institutional, Research Grant AstraZeneca;Financial Interests, Institutional, Research Grant Eurocept-pharmaceuticals;Financial Interests, Institutional, Research Grant Pfizer;Financial Interests, Institutional, Research Grant Genentech;Non-Financial Interests, Institutional, Other Genentech;Financial Interests, Institutional, Research Grant Merck;Non-Financial Interests, Institutional, Other Merck;Financial Interests, Institutional, Research Grant Novartis;Non-Financial Interests, Institutional, Other Novartis;Financial Interests, Institutional, Research Grant Roche;Non-Financial Interests, Institutional, Other Roche;Financial Interests, Institutional, Research Grant Tesaro;Non-Financial Interests, Institutional, Other Tesaro;Financial Interests, Institutional, Research Grant Immunomedics;Non-Financial Interests, Institutional, Other Immunomedis;Non-Financial Interests, Institutional, Other AstraZeneca;Non-Financial Interests, Institutional, Oth r Pfizer;Non-Financial Interests, Institutional, Other Cergentis;Non-Financial Interests, Institutional, Other Daiichi Sankyo;Non-Financial Interests, Institutional, Other IBM;Non-Financial Interests, Institutional, Other Bayer. All other authors have declared no conflicts of interest.