PIK3CA Q75E

Alpelisib selectively inhibits the p110α catalytic subunit of PI3Kα and is approved for treatment of breast cancers harboring canonical PIK3CA mutations...Structural analyses revealed plausible mechanisms for the functional phenotypes of the majority of the noncanonical PIK3CA mutations. Collectively, these findings highlight the importance of characterizing the function of noncanonical PIK3CA mutations and suggest that patients with HNSCC whose tumors harbor activating noncanonical PIK3CA mutations may benefit from treatment with PI3Kα inhibitors.

Cohort A: HR+/HER2- pts receiving fulvestrant (FUL) alone (n = 124) or ALP/FUL (n = 111) in treatment line ≥2L were considered in survival analysis . This study validates the activity of ALP among a diverse real world population, showing pts with PIK3CA mutations have longer rwPFS on ALP/FUL than FUL alone . Pts with SOLAR1m were more likely to be treated with ALP- and tended to be treated in earlier line setting- than pts with OTHERm . No consistent effect in a small subset of pts with OTHERm treated with ALP was observed, but there is evidence that OTHERm may differ in their degree of PI3K activation, oncogenicity, and ALP sensitivity .