Ipatasertib-fulvestrant combination extends PFS after CDK4/6 inhibitor failure in ER+/HER2- metastatic breast cancer

Results from the phase 3 FINER trial showed that combining ipatasertib with fulvestrant significantly prolongs progression-free survival (PFS) in participants with oestrogen receptor (ER)-positive, human epidermal growth factor 2 (HER2)-negative metastatic breast cancer who have progressed after prior aromatase inhibitor and CDK4/6 inhibitor therapy.

The phase 3 FINER trial (NCT04650581) enrolled 250 participants with stage 4 ER-positive/HER2-negative breast cancer, who had previously received both an aromatase inhibitor and a CDK4/6 inhibitor. Participants were randomised 1:1 to receive either ipatasertib or placebo, both in combination with fulvestrant, and the results were presented by Prof. Stephen K.L. Chia (University of British Columbia, Canada) [1].

In the intention-to-treat population, the median PFS per investigator assessment was 5.32 months with the ipatasertib-fulvestrant combination compared to 1.94 months in the placebo arm (HR 0.61; 95% CI 0.46–0.81; P=0.0007). By blinded independent central review, the median PFS was 9.07 months compared with 3.71 months (HR 0.65; 95% CI 0.46–0.93; P=0.0177). The median overall survival in the intention-to-treat population was not significantly different at the time of reporting: 23.13 months in the ipatasertib arm versus 24.87 months in the placebo group (HR 1.07; 95% CI 0.68–1.69; P=0.75), with data maturity at 50%.

Regarding subsets, participants with tumours harbouring AKT pathway alterations presented with markedly improved PFS by blinded independent central review in the ipatasertib arm: 12.88 months versus 3.68 months (HR 0.50; 95% CI 0.29–0.87; P=0.011). In this subset, PFS per RECIST 1.1 criteria was 5.45 versus 1.91 months (HR 0.47; 95% CI 0.31–0.72; P=0.0005).

Exploratory analyses in the oestrogen receptor 1 (ESR1) wild-type subgroup (n=128) showed a median PFS of 5.55 months with the combination compared to 2.00 months for placebo (HR 0.54; 95% CI 0.36–0.83). In participants with ESR1 mutations (n=122), PFS was 3.71 versus 1.87 months (HR 0.61; 95% CI 0.41–0.91).

Adverse events associated with ipatasertib included diarrhoea (87.1%), nausea (58.9%), hyperglycaemia (43.6%), and fatigue (40.3%). Grade 3 diarrhoea arose in 16.1%, and treatment discontinuation due to adverse events in 6.5% of participants on ipatasertib compared with 0% and 0.8% on placebo, respectively.

“The ipatasertib-fulvestrant combination was generally well-tolerated and offers a promising option for patients following progression on standard endocrine and CDK4/6 inhibitor therapy,” Prof. Chia concluded, highlighting its relevance for a patient population with limited post-CDK4/6 treatment choices.

1. Chia SKL, et al. A double-blind placebo controlled randomized phase III trial of fulvestrant and ipatasertib as treatment for advanced HER2-negative and estrogen receptor positive (ER+) breast cancer following progression on first line CDK 4/6 inhibitor and aromatase inhibitor: The CCTG/BCT MA.40/FINER study (NCT04650581). Abstract LBA1005, ASCO Annual Meeting 2025, 30 May–3 June, Chicago, IL, USA.

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Posted on 30 July 202530 July 2025