New combination therapy trial provides hope for breast cancer patients

Combining AKT protein kinase inhibitors with hormone therapy can help prolong the lives of patients with a common breast cancer, according to an ongoing clinical trial.

The FAKTION study found that patients with a cancer mutation that activated the AKT protein linked to cell survival and metabolism lived for around 39 months when given a combination of capivasertib and the hormone treatment fulvestrant. This compared to 20 months of life among patients who were prescribed the hormone and a placebo, while the combined capivasertib-fulvestrant therapy also doubled the amount of time that the cancers were under control – from five months to 10.

More than two thirds of advanced breast cancer sufferers have oestrogen receptor-positive (ER-positive), HER-2 negative disease, and endocrine-based therapy is generally employed before chemotherapy in most of those cases. However, since the vast majority of tumours eventually become resistant to endocrine treatments, new approaches are always being considered in a bid to extend life.

Writing in The Lancet, researchers said that follow-up analysis five years into the trial “showed that capivasertib addition to fulvestrant extends the survival of participants with aromatase inhibitor-resistant ER-positive, HER2-negative advanced breast cancer.”

The report authors also noted that neither alpelisib nor everolimus – the two drugs that inhibit the P13K/AKT/PTEN pathway currently approved by regulators – significantly extend overall survival compared to endocrine treatment alone. However, the fact that capivasertib “is a potent and selective inhibitor of all three AKT isoforms (AKT1, AKT2, and AKT3)” offers hope that it might become an effective option against (ER-positive), HER-2 negative strains.

“The mature overall survival data reported (in the FAKTION report) show that capivasertib has potential to fill this treatment gap,” states the report. It also draws attention to the potential for using Next Generation Sequencing (NGS) technology to determine which patients might benefit most from using the new combination therapy, since capivasertib “predominantly benefited participants with PI3K/AKT/PTEN pathway-altered tumours.”

The multi-centre, double-blind trial was carried out by Cardiff University, Velindre University NHS Trust and AstraZeneca, the developer of capivasertib. Study co-leader, Professor Rob Jones, hailed the results as “very exciting.”

“Not only have we shown that capivasertib has the potential to give patients a very significant extension in their lifespan, but we may also be able to select out those patients who are most likely to benefit from the treatment by carrying out genetic tests on their cancer tissue," he added.

“We are now very keen to see if this is confirmed in a larger phase three trial which has already completed recruitment.”