Multinational phase 3 trial of gedatolisib plus fulvestrant with or without palbociclib for HR+/HER2-/PIK3CA wild type advanced breast cancer

The multinational phase 3 VIKTORIA-1 trial evaluated gedatolisib, palbociclib, and fulvestrant (gedatolisib triplet) and gedatolisib plus fulvestrant (gedatolisib doublet) compared with fulvestrant monotherapy in patients with HR-positive, HER2-negative, PIK3CA wild-type advanced breast cancer, with disease progression during or after CDK4/6 inhibitor and aromatase inhibitor therapy. Progression-free survival was the primary endpoint. A total of 392 patients were randomized (1:1:1). The median follow-up was 10.1 months. The median progression-free survival was 9.3 months in the gedatolisib-triplet group and 2.0 months in the fulvestrant monotherapy group (HR 0.24; p<0.001) and 7.4 months in the gedatolisib-doublet group (versus fulvestrant monotherapy HR 0.33; p<0.001). Grade ≥ 3 treatment-related adverse events in the gedatolisib groups were neutropenia, stomatitits, rash, hyperglycemia, and diarrhea, and leaded to discontinuation in 2.3% of patients in the triplet group and 3.1% of patients in the doublet group. The authors conclude that the addition of gedatolisib to fulvestrant, with or without palbociclib, significantly reduced the risk of disease progression or death in patients with HR-positive/HER2-negative/PIK3CA wild-type advanced breast cancer.