Inavolisib + Palbo–Fulvestrant Adds 7 mo OS Benefit in PIK3CA-Mut HR+/HER2- mBC

Inavolisib, a PI3Kα-selective inhibitor, was combined with palbociclib and fulvestrant in the double-blind, randomized Phase 3 INAVO120 trial (NCT04191499). The trial population included 325 CDK4/6-naïve patients with a PIK3CA-mutation in HR-positive, HER2-negative locally advanced/metastatic breast cancer relapsing ≤12 mo after adjuvant endocrine therapy (expected to be about 40% of these patients). The triplet delivered a median OS of 34.0 mo versus 27.0 mo for placebo + palbociclib-fulvestrant (HR 0.67, p = 0.02); ORR was 62.7% (n = 161) vs 28.0% (n = 164), and the updated PFS HR was 0.42. Grade ≥3 hyperglycemia (≈15%), stomatitis, diarrhea, and ocular events drove 6.8% discontinuations, which is comparable to the 36.6% grade ≥3 hyperglycemia and 21% discontinuations seen with alpelisib + fulvestrant in SOLAR-1, which showed no significant OS gain.