TRUQAP combined with fulvestrant significantly improves progression-free survival in HR+/HER2− metastatic breast cancer with *PIK3CA/AKT1/PTEN* alterations.

Efficacy in Genetically Altered Breast Cancer

In the CAPItello-291 trial, TRUQAP plus fulvestrant demonstrated a median progression-free survival (PFS) of 7.3 months versus 3.1 months with placebo in patients harboring *PIK3CA/AKT1/PTEN* alterations (HR 0.50, p<0.0001). The objective response rate (ORR) was 26% (vs. 8% placebo), with a median duration of response (DoR) of 10.2 months. Efficacy was driven by AKT pathway inhibition, targeting tumors resistant to endocrine therapy. Patients with wild-type genes showed no statistically significant benefit. The combination is indicated post-endocrine therapy progression or recurrence within 12 months of adjuvant therapy. Overall survival data remain immature. Clinical response correlates with genetic alterations detected via FDA-approved companion diagnostics.