Gedatolisib in HR+/HER2− PIK3CA wild-type breast cancer: median PFS 9.3 vs 2.0 months in phase 3

In the phase 3 VIKTORIA-1 trial (n=392), the triplet of gedatolisib, palbociclib and fulvestrant extended median progression-free survival to 9.3 months versus 2.0 months with fulvestrant alone (HR 0.24; 95% CI 0.17-0.35) in HR+/HER2− advanced breast cancer without a PIK3CA mutation, after progression on a CDK4/6 inhibitor. The objective response rate was 31.5% versus 1%, with a median duration of response of 17.5 months; the gedatolisib–fulvestrant doublet reached 7.4 months PFS (HR 0.33). Toxicity is the trade-off: grade ≥3 neutropenia in 62.3% of the triplet arm and stomatitis in 19.2%, with discontinuation for adverse events in 2.3-3.1%. It is the first phase 3 trial in which blocking the PI3K/AKT/mTOR pathway produced a significant benefit in the PIK3CA wild-type population, which until now had no targeted option.