Adding venetoclax to fulvestrant offers no extra benefit in VERONICA trial
medwireNews: Adding the BCL2 inhibitor venetoclax to fulvestrant does not improve outcomes for women with estrogen receptor-positive, HER2-negative locally advanced breast cancer resistant to endocrine and CDK4/6 inhibitor treatment, say the VERONICA investigators.
The phase 2 trial included patients who had no more than two prior lines of hormone therapy without chemotherapy and had experienced disease recurrence or progression on palbociclib or ribociclib, explained Geoffrey Lindeman (Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia) at the 2021 ASCO Annual Meeting.
The primary endpoint of clinical benefit rate (CBR) was a comparable 11.8% for the 51 patients randomly assigned to receive venetoclax 800 mg/day plus fulvestrant 500 mg every 28 days after an initial loading dose, and 13.7% for the 52 patients given fulvestrant alone.
After a median 9.9 months of follow-up, intention-to-treat analysis of the combination and fulvestrant-only groups showed similar progression-free survival (PFS, median 2.69 vs 1.94 months).
While the overall survival (OS) endpoint is yet to mature, the initial analysis did not favor venetoclax over fulvestrant alone (median 16.76 months vs unreached, significant hazard ratio [HR]=2.56), and an updated analysis in April 2021 again gave a lower, nonsignificant HR of 1.85, Lindeman commented.
There was an imbalance in deaths between the two treatment groups, at 19 with venetoclax use and nine with fulvestrant alone, which Lindeman attributed to disease progression more than 28 days after the last dose of venetoclax.
Finally, there was no significant difference in CBR and PFS among patients taking venetoclax plus fulvestrant versus fulvestrant alone when stratifying patients by high and low BCL2 tumor expression, but exploratory analysis uncovered a trend toward improved PFS with venetoclax use among patients with PIK3CA wild-type tumors.
Lindeman concluded that while venetoclax plus fulvestrant had a safety profile “consistent” with previous reports, “it remains unclear whether BCL2 inhibitor would be effective in an endocrine therapy-responsive, CDK4/6 inhibitor-naïve treatment setting.”
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