Ipatasertib Triplet Doubles PFS in PI3K/AKT/PTEN-Mutant HR+/HER2- Metastatic Breast Cancer After CDK4/6

Ipatasertib—the oral pan-AKT inhibitor—was tested in the Phase Ib TAKTIC trial (NCT03959891) alongside fulvestrant ± palbociclib in 77 pre-treated, CDK4/6-exposed HR+/HER2- MBC patients. In the 20-patient triplet cohort with baseline NGS, tumors harboring pathway mutations (PIK3CA, AKT1, or PTEN; n = 9) achieved a median PFS of 505 days (16.6 mo) versus 114 days (3.8 mo) for wild-type disease (HR 0.20, p = 0.015). FGFR1 amplification independently predicted rapid progression (HR 5.42). Overall, PI3K/AKT/PTEN alterations were present in 60% of patients and ESR1 in 25% patients, while RAS/FGFR1/ERBB2 changes trended toward resistance. Toxicities mirrored prior ipatasertib data with manageable diarrhea and rash. By comparison, the capivasertib + fulvestrant CAPItello-291 regimen prolonged PFS to 7.2 mo vs 3.1 mo for fulvestrant alone, and everolimus + exemestane delivers ~7.8 mo—highlighting the pronounced benefit in genomically selected patients here.

https://aacrjournals.org/clincancerres/article/31/12_Supplement/P2-01-17/753340/Abstract-P2-01-17-Genomic-predictors-of-response