Adding the BCL2 inhibitor venetoclax to fulvestrant did not improve clinical benefit rates (CBR) or PFS in women with oestrogen receptor-positive, HER2-negative locally advanced breast cancer compared to fulvestrant alone, new research from Australia reveals.
Presenting the findings from the phase II VERONICA trial at ASCO this week lead investigator Professor Geoffrey Lindeman from the Walter and Eliza Hall Institute in Melbourne said the trial looked at 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.
Some 103 patients were randomised to receive either venetoclax 800mg/day plus fulvestrant 500mg on a 28 -day cycle or fluvestrant alone.
But while the overall survival data is yet to mature, Professor Lindeman said the initial analysis based on a median 9.9 months follow-up, does not favour the combination therapy.,
The clinical benefit rate (CBR) was 11.8% (95% CI, 4.44%-23.87%) with venetoclax/fulvestrant versus 13.7% (95% CI, 5.7%-26.26%) with fulvestrant alone, translating to a risk difference of -1.96% (95% CI, -16.86%-12.94%).
Adverse events were higher in the combination therapy arm with 26% experiencing at least one grade 3 or 4 adverse event compared to 11.4% in the fulvestrant only arm.
The majority of AEs, including all-grade nausea (64% of patients) and diarrhoea (54%), were ‘anticipated’ Professor Lindeman says, noting the events were previously attributed to either agent and all low grade and readily treated.
While few AE’s led to drug withdrawal about 44% of patients in the the combination therapy arm required dose modification or therapy interruption he also said.
The combination and fulvestrant-only groups also showed similar progression-free survival (median 2.69 vs 1.94 months) – a similarity that persisted when investigators stratified patients by high and low BCL2 tumour expression.
But an exploratory analysis uncovered a trend towards improved PFS in patients with PIK3CA wild type tumours he added.
“For the 60 patients in the PICK3CA wild type subgroup CBR was 20.7% in the venetoclax plus fulvestrant arm vs 9.7% in the fulvestrant only arm the median PFS was 3.7 months vs 1.9 months respectively in these groups”.
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.
While venetoclax plus fulvestrant had a safety profile “consistent” with previous reports, Professor Lindeman said “it remains unclear whether the BCL2 inhibitor would be effective in an endocrine therapy-responsive, CDK4/6 inhibitor-naïve treatment setting.”