Are there scenarios where you would consider use of capivasertib for non-AKT pathway altered patients given the efficacy seen in the overall treatment population of the CAPItello-291 trial?  

While PFS curves are similar in AKT-altered and the overall population, PFS curves are much closer (HR 0.79, 0.61-1.02) in patients with AKT pathway non-altered tumors excluding unknown NGS results (Fig S2), suggesting that the majority of the efficacy is from the AKT-altered population (CAPItello-2...

Whereas CAPItello-291 showed improved PFS in the overall population and in the subgroup with alterations in the AKT pathway, there was no significant difference in PFS for patients who had a tumor that did not have an alteration in the AKT pathway. For patients with known NGS results showing an AKT ...

In the presence of preclinical data showing inhibition of growth by capivasertib in some cell lines without AKT pathway gene alterations (Davies et al., PMID 22294718) and the ample preclinical data demonstrating possibilities of aberrant AKT pathway signaling due to other mechanisms (He et al., PMI...