No OS improvement over chemo from capivasertib plus paclitaxel in advanced TNBC

Dr Heather McArthur - UT Southwestern Medical Center, Dallas, USA

The CAPItello-290 study was based on two phase II studies, the LOTUS and the PACT studies, that showed promising activity with AKT pathway targeting. CAPItello-290 was a global phase III randomised study that enrolled 812 patients with untreated metastatic triple negative breast cancer and randomised them to receive first line paclitaxel with either capivasertib, an AKT targeting oral agent that targets all three AKT isoforms, or placebo with paclitaxel. There were two primary endpoints for this study – overall survival in the overall population, so the population was not selected by any biomarkers, but there was a coprimary endpoint for patients with AKT1, PTEN or PIK3CA mutations.

The study did not meet the primary endpoints in either the intention to treat overall population for overall survival or in the altered population. In terms of key secondary endpoints there was a numerical trend toward improvement in progression free survival and overall response rate in favour of capivasertib with paclitaxel in the altered population but overall this was a negative study.

What impact might these results have on future studies?

It was a high bar to have overall survival as a primary endpoint, and dual primary endpoints, which of course could be impacted by imbalances in subsequent lines of therapy. So we will be looking at subsequent lines of therapy in both arms. But it does indicate that potentially the AKT pathway was not as important in driving triple negative breast cancer as was previously thought.