Fulvestrant plus vandetanib versus placebo for the treatment of patients with metastatic breast cancer resistant to aromatase inhibitor therapy (FURVA): a multicentre, Phase 2, randomised controlled trial

Beresford, Mark, Casbard, Angela ORCID: https://orcid.org/0000-0001-6241-3052, Hudson, Zoe, Carucci, Margherita, Ingarfield, Kate, Gee, Julia ORCID: https://orcid.org/0000-0001-6483-2015, Smith, Joanna ORCID: https://orcid.org/0000-0003-4234-6686, Kitson, Terri ORCID: https://orcid.org/0000-0001-6333-046X, Alchami, Fouad, Madden, Tracie-Ann ORCID: https://orcid.org/0000-0001-7880-7873, Hayward, Larrie, Hwang, David, Spensley, Saiqa, Waters, Simon, Wheatley, Duncan and Jones, Robert H. ORCID: https://orcid.org/0000-0003-3576-9496 2023. Fulvestrant plus vandetanib versus placebo for the treatment of patients with metastatic breast cancer resistant to aromatase inhibitor therapy (FURVA): a multicentre, Phase 2, randomised controlled trial. BJC Reports 1 (1) , 13. 10.1038/s44276-023-00016-8

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Abstract

Background: FURVA, a randomised, double-blind Phase II trial, investigated whether the addition of vandetanib to fulvestrant improved progression-free survival (PFS) in patients with an aromatase inhibitor(AI)-resistant advanced breast cancer. Methods: Postmenopausal women with oestrogen receptor-positive (ER+ve)/HER2-negative advanced breast cancer, who experienced disease progression on an AI, were randomised (1:1) to fulvestrant 500 mg (Q28) with vandetanib 300 mg od (f + v) or placebo (f + p) until disease progression or discontinuation. The primary endpoint was PFS; secondary endpoints included overall survival (OS) and the influence of REarranged during Transfection (RET) signalling on outcomes. Results: In total, 165 participants were randomised to f + v (n = 80) or f + p (n = 85). Median PFS was 5.5 months (m) for f + v compared to 5.5 m for f + p (hazard ratio (HR) 0.88; 95% CI: 0.62–1.23; P = 0.22). Unexpectedly, high total RET expression was associated with a PFS advantage of 8.87 m vs 3.94 with low RET (HR 0.493: 95% CI 0.32–0.77; P = 0.002) independent of the treatment arm, supported by an OS advantage 21.95 m vs 18.04 (HR 0.584; 95% CI 0.34–1.00; P = 0.051) in the high-RET group. Conclusion: The addition of vandetanib to fulvestrant does not improve PFS. However, high total RET expression was associated with improved PFS, suggesting RET may have a prognostic role in patients treated with fulvestrant. Clinical trial registration: ClinicalTrials.gov, NCT02530411.

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Medicine Pharmacy Centre for Trials Research (CNTRR)
Additional Information:	License information from Publisher: LICENSE 1: URL: http://creativecommons.org/licenses/by/4.0/, Type: open-access
Publisher:	Nature Publishing Group UK
ISSN:	2731-9377
Funders:	Cancer Research UK
Date of First Compliant Deposit:	15 September 2023
Date of Acceptance:	21 August 2023
Last Modified:	30 Oct 2023 18:47
URI:	https://orca.cardiff.ac.uk/id/eprint/162556

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