Back to Journals » Therapeutics and Clinical Risk Management » Volume 17

Role of Alpelisib in the Treatment of PIK3CA-Mutated Breast Cancer: Patient Selection and Clinical Perspectives

Authors Chang DY, Ma WL, Lu YS

Received 1 December 2020

Accepted for publication 16 February 2021

Published 5 March 2021 Volume 2021:17 Pages 193—207


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Professor Deyun Wang

Dwan-Ying Chang,1 Wei-Li Ma,1,2 Yen-Shen Lu1

1Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan; 2Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan

Correspondence: Yen-Shen Lu
Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan
Email [email protected]

Abstract: The PI3K/AKT/mTOR pathway has long been known to play a major role in the growth and survival of cancer cells. Breast tumors often harbor PIK3CA gene alterations, which therefore constitute a rational drug target. However, it has taken many years to demonstrate clinically-relevant efficacy of PI3K inhibition and eventually attain regulatory approvals. As data on PI3K inhibitors continue to mature, this review updates and summarizes the current state of the science, including the prognostic role of PIK3CA alterations in breast cancer; the evolution of PI3K inhibitors; the clinical utility of the first-in-class oral selective PI3Kα inhibitor, alpelisib; PIK3CA mutation detection techniques; and adverse effect management. PIK3CA-mutated breast carcinomas predict survival benefit from PI3K inhibitor therapy. The pan-PI3K inhibitor, buparlisib and the beta-isoform-sparing PI3K inhibitor, taselisib, met efficacy endpoints in clinical trials, but pictilisib did not; moreover, poor tolerability of these three drugs abrogated further clinical trials. Alpelisib is better tolerated, with a more manageable toxicity profile; the principal adverse events, hyperglycemia, rash and diarrhea, can be mitigated by intensive monitoring and timely intervention, thereby enabling patients to remain adherent to clinically beneficial treatment. Alpelisib plus endocrine therapy shows promising efficacy for treating postmenopausal women with HR+/HER2– advanced breast cancer. Available evidence supporting using alpelisib after disease progression on first-line endocrine therapy with or without CDK4/6 inhibitors justifies PIK3CA mutation testing upon diagnosing HR+/HER2– advanced breast cancer, which can be done using either tumor tissue or circulating tumor DNA. With appropriate toxicity management and patient selection using validated testing methods, all eligible patients can potentially benefit from this new treatment. Further clinical trials to assess combinations of hormone therapy with PI3K, AKT, mTOR, or CDK 4/6 inhibitors, or studies in men and women with other breast subtypes are ongoing.

Keywords: HR+/HER2− advanced/metastatic breast cancer, PIK3CA mutation test, alpelisib PI3K alpha-selective inhibitor, prognosis, survival benefit, toxicity management

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]