Fulvestrant plus capivasertib versus placebo after relapse or progression on an aromatase inhibitor in metastatic, oestrogen receptor-positive, HER2-negative breast cancer (FAKTION): overall survival, updated progression-free survival, and expanded biomarker analysis from a randomised, phase 2 trial

Howell, Sacha J., Casbard, Angela ORCID: https://orcid.org/0000-0001-6241-3052, Carucci, Margherita, Ingarfield, Kate, Butler, Rachel, Morgan, Sian, Meissner, Magdalena, Bale, Catherine, Bezecny, Pavel, Moon, Sarah, Twelves, Chris, Venkitaraman, Ramachandran, Waters, Simon, De Bruin, Elza C., Schiavon, Gaia, Foxley, Andrew and Jones, Robert H. ORCID: https://orcid.org/0000-0003-3576-9496 2022. Fulvestrant plus capivasertib versus placebo after relapse or progression on an aromatase inhibitor in metastatic, oestrogen receptor-positive, HER2-negative breast cancer (FAKTION): overall survival, updated progression-free survival, and expanded biomarker analysis from a randomised, phase 2 trial. The Lancet Oncology 23 (7) , pp. 851-864. 10.1016/s1470-2045(22)00284-4

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Abstract

Background Capivasertib, an AKT inhibitor, added to fulvestrant, was previously reported to improve progression-free survival in women with aromatase inhibitor-resistant oestrogen receptor (ER)-positive, HER2-negative advanced breast cancer. The benefit appeared to be independent of the phosphoinositide 3-kinase (PI3K)/AKT/phosphatase and tensin homologue (PTEN) pathway alteration status of tumours, as ascertained using assays available at the time. Here, we report updated progression-free survival and overall survival results, and a prespecified examination of the effect of PI3K/AKT/PTEN pathway alterations identified by an expanded genetic testing panel on treatment outcomes. Methods This randomised, multicentre, double-blind, placebo-controlled, phase 2 trial recruited postmenopausal adult women aged at least 18 years with ER-positive, HER2-negative, metastatic or locally advanced inoperable breast cancer and an Eastern Cooperative Oncology Group performance status of 0–2, who had relapsed or progressed on an aromatase inhibitor, from across 19 hospitals in the UK. Participants were randomly assigned (1:1) to receive intramuscular fulvestrant 500 mg (day 1) every 28 days (plus a 500 mg loading dose on day 15 of cycle 1) with either capivasertib 400 mg or matching placebo, orally twice daily on an intermittent weekly schedule of 4 days on and 3 days off, starting on cycle 1 day 15. Treatment continued until disease progression, unacceptable toxicity, loss to follow-up, or withdrawal of consent. Treatment was allocated by an interactive web-response system using a minimisation method (with a 20% random element) and the following minimisation factors: measurable or non-measurable disease, primary or secondary aromatase inhibitor resistance, PIK3CA status, and PTEN status. The primary endpoint was progression-free survival in the intention-to-treat population. Secondary endpoints shown in this Article were overall survival and safety in the intention-to-treat population, and the effect of tumour PI3K/AKT/PTEN pathway status identified by an expanded testing panel that included next-generation sequencing assays. Recruitment is complete. The trial is registered with ClinicalTrials.gov, number NCT01992952.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences Centre for Trials Research (CNTRR) Medicine European Cancer Stem Cell Research Institute (ECSCRI)
Additional Information:	This is an Open Access article under the CC BY 4.0 license.
Publisher:	Elsevier
ISSN:	1470-2045
Date of First Compliant Deposit:	14 June 2022
Last Modified:	29 Jun 2023 08:58
URI:	https://orca.cardiff.ac.uk/id/eprint/150340

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