Inavolisib Adds 7 Months OS atop Palbo-Fulvestrant in PIK3CA-Mutant HR⁺/HER2- MBC

In the Phase 3 double-blind INAVO120 trial (NCT04191499), 161 women with endocrine-resistant, PIK3CA-mutated HR+⁺/HER2- metastatic breast cancer received the PI3Kα inhibitor inavolisib plus palbociclib-fulvestrant; 164 got placebo with the same CDK4/6–SERD backbone. After 34 mo median follow-up, median OS was 34.0 mo vs 27.0 mo(HR 0.67, p = 0.02). ORR hit 63% vs 28%, and updated PFS HR was 0.42. Grade ≥3 hyperglycemia (all-grade 25%, ≥G3 7%), stomatitis/mucositis, diarrhea and ocular AEs were more frequent, leading to drug discontinuation in 6.8% versus 0.6%. Alpelisib-fulvestrant in SOLAR-1 (NCT02437318) achieved only a non-significant OS trend (39.3 vs 31.4 mo; HR 0.86) with higher rates of grade 3–4 hyperglycemia (~37%) and rash (~9%).