Vandetanib Addition Fails To Extend Aromatase Inhibitor-Resistant Breast Cancer Survival

Author: By Lynda Williams, Senior medwireNews Reporter 

medwireNews: Use of the multikinase inhibitor vandetanib alongside fulvestrant does not improve survival for postmenopausal women with advanced oestrogen receptor (ER)-positive breast cancer that is resistant to aromatase inhibitor therapy, FURVA trial results show. 

Robert Jones, from Cardiff University in the UK, explained at the ESMO Virtual Congress 2020 that vandetanib targets RET, VEGFR2 and VEGFR3, potentially combating mechanisms of resistance associated with endocrine therapy. 

The study recruited patients with locally advanced unresectable or metastatic ER-positive, HER2-negative breast cancer who had relapsed on aromatase inhibitor therapy and had received up to one line of chemotherapy and three lines of endocrine therapy for metastatic disease. 

The primary endpoint of median progression-free survival (PFS) in the intention-to-treat population was 5.5 months for both the 80 participants who were randomly assigned to receive vandetanib 300 mg/day alongside fulvestrant 500 mg on days 1 and 15 of the first 28-day cycle, and day 1 thereafter, and the 85 patients instead given placebo with fulvestrant. 

Nor did overall survival (OS) significantly differ between the vandetanib and placebo treatment arms, at a median of 19.5 and 19.9 months, respectively, the investigator said. 

However, preplanned analysis indicated that patients with baseline high RET protein expression – defined as a tumour epithelial cell H-score over 166 – may have a significantly better response to fulvestrant than those with low RET expression, with or without use of vandetanib. 

Among the 115 patients whose RET expression was characterised in their primary tissue sample, high versus low RET expression was associated with significantly better PFS (median 8.87 vs 3.94 months, hazard ratio [HR]=0.493) and a trend towards improved OS (median 21.95 vs 18.04 months, HR=0.584) over up to 50 months of follow-up.  

“The data is suggestive that high RET expression may predict for improved outcomes on fulvestrant therapy in aromatase inhibitor resistant disease”, Robert Jones suggested, but he noted that the “findings require additional validation.” 

Reference 

Jones R, Casbard A, Carucci M, et al. Vandetanib plus fulvestrant versus placebo plus fulvestrant after relapse or progression on an aromatase inhibitor in metastatic ER positive breast cancer (FURVA): A randomised, double-blind, placebo-controlled, phase II trial. Ann Oncol 2020; 31 (Suppl_4): S1142–S1215. DOI: 10.1016/annonc/annonc325.