FINER Study Points to Benefits from Ipatasertib in Treatment-Resistant Hormone Sensitive Breast Cancer

For people with hormone-receptor-positive breast cancer whose disease has spread despite treatment with hormone-blocking therapy, the standard treatment approach so far has been simply to continue with different forms of hormone therapy. 

Now a study suggests that also targeting a key cell-growth pathway with a drug called ipatasertib in these patients, could achieve significant improvements in progression-free survival compared to hormone therapy alone.  

One of the mechanisms by which breast cancers develop resistance to hormone therapy is mutations in genes coding for the PI3K/AKT pathway, which is a cell signalling pathway essential for cell growth. Dysfunctions in this pathway are implicated in a range of diseases including cancer.  

Ipatasertib is an AKT inhibitor, which means it specifically targets the same AKT pathway in cancer cells and disrupts it, which stops cancer cells from replicating. 

The FINER study involved 250 people from Australia, Canada and New Zealand with oestrogen receptor-positive, HER2-negative breast cancer. All those in the study had already received treatment with the standard dual therapy of a CDK4/6 inhibitor plus an aromatase inhibitor, but their cancer had spread.  

The participants were randomised to either receive treatment with ipatasertib plus the standard hormone therapy drug fulvestrant, or fulvestrant plus a placebo. After around 15 months of follow-up, researchers found evidence suggesting that the ipatasertib therapy was significantly slowing down progression of the cancer.  

Those who were treated with ipatasertib plus fulvestrant had a median of 5.3 months before their disease progressed, compared to a median of 1.9 months in the group treated with fulvestrant only. 

Researchers also looked at a subset of participants whose tumours showed evidence of having a mutation in the AKT pathway, and compared their outcomes after ipatasertib treatment with those of participants without those mutations. This revealed that the AKT pathway altered patients had a median of 5.45 months before their disease progressed, compared to 1.9 months in the unaltered group. 

There was a higher rate of side effects in the ipatasertib group, with 16% of patients experiencing diarrhoea compared to none of the placebo group, 3% experiencing fatigue, 2% experiencing vomiting, and 2% reporting rash.  

The research team said the results suggest that adding ipatasertib to standard therapy for this patient group significantly prolongs progression-free survival compared to standard therapy alone, but more follow-up and analysis is needed to understand the longer-term effects, and how the combination works with different breast cancer subtypes. 

Publication: 

Chia SKL, Redfern AD, Ayoub J-BM, Chalchal HI, Rayson D, Rushton M, Desbiens C, Sabanathan D, Raphael J, Chan A, Singh J, Simmons CE, Zdenkowski N, Wilson S, Rodin D, Cescon DW, Schimmoller F, Gallinaro L, Chen BE, Paralekar WR. 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). Journal of Clinical Oncology. 2025; 43 (suppl 17).  Abstract LBA1005.