In advanced prostate cancer, combining ipatasertib with abiraterone improved progression-free survival compared to abiraterone alone.
Interim results from a Phase III trial have demonstrated that in men with advanced prostate cancer, combing the anti-androgen, abiraterone with ipatasertib, extends the time before disease progression. In men with prostate cancer, inactivation of the PTEN tumour suppressor gene can be found in up to 50% of castration-resistant tumours. Loss of PTEN function leads to activation of the AKT pathway and is strongly associated with adverse patient outcomes. Ipatasertib is a potent and novel, inhibitor of ATK, which is is one of the most frequently activated protein kinases in human cancers and which plays a critical role in tumour growth, proliferation, survival as well as resistance to anticancer therapy. Thus adding ipatasertib to a treatment regime with abiraterone, simultaneously targets two of the aberrant pathways in prostate cancer. This is particularly important given that metastatic castrate-resistant prostate cancer has a poor prognosis.
Findings
In total, 554 (50%) men were assigned to the placebo–abiraterone group and 547 (50%) to the ipatasertib–abiraterone group and the median follow-up duration was 19 months. Among 261 men in the placebo–abiraterone group and 260 in the ipatasertib–abiraterone group), median radiographical progression-free survival was 16·5 months (95% CI 13·9–17·0) in the placebo group and 18·5 months (16·3–22·1) in the ipatasertib–abiraterone group. This equates to a 23% reduction in the risk of disease progression (hazard ratio, HR = 0.77, 95% CI 0.61 – 0.98, p = 0.04).
Although this is an ongoing trial, the authors of this interim analysis concluded that the combined AKT and androgen-receptor signalling pathway inhibition with ipatasertib and abiraterone is a potential treatment for men with PTEN-loss metastatic castrate-resistant prostate cancer, a population with a poor prognosis.
Citation
Sweeney C et al. Ipatasertib plus abiraterone and prednisolone in metastatic castration-resistant prostate cancer (IPATential150): a multicentre, randomised, double-blind, phase 3 trial. Lancet 2021
