IPAT on the back.

Top Line: PTEN is one of the most frequently mutated genes in prostate cancer, which often results in dysregulation of the PI3K/AKT pathway.

The Study: Ipatasertib is an AKT inhibitor. IPATential150 was a large randomized phase 3 trial that sought to determine if adding ipatasertib to abiraterone in first-line treatment of mCRPC would improve radiographic progression-free survival (PFS). Over 1100 men with mCRPC were randomized to abiraterone +/- ipatasertib and underwent CT/MRI and bone scan every 2-3 months. PTEN loss at baseline was defined as 50% or more of tumor specimen having no PTEN staining on immunohistochemistry, which was present in 47% of enrollees. Co-primary endpoints were radiographic PFS in 1) the overall population and 2) the subset of men with PTEN loss. In the overall group, there was no significant difference in outcomes with PFS events occurred in 55% of those receiving abiraterone versus 46% of those receiving abiraterone + ipatasertib (median time to event was 17 versus 19 months, respectively). However, among those with PTEN loss, the difference creeped up to significance with rates of 59% versus 48% (median time to event, again, was 17 versus 19 months). Can a reader get a RMST here? Anyway, PFS improvements and other clinical measures of response with ipatasertib were more pronounced among patients found to have PTEN loss on next-gen sequencing and when PTEN loss was seen in a higher % of tumor specimen. The main additional side effects of ipatasertib were diarrhea, rash, and hyperglycemia.

TBL: The addition of the AKT inhibitor ipatasertib to first-line abiraterone improves radiographic PFS among men with mCRPC and PTEN loss. | Sweeney, Lancet 2021