VJToday

FDA approves gedatolisib for HR+/HER2–, PIK3CA wild-type breast cancer

On July 14, 2026, the U.S. Food and Drug Administration (FDA) granted approval to gedatolisib, a pan-PI3K/mTOR inhibitor, in combination fulvestrant with or without palbociclib for patients with HR+/HER2-/PIK3CA wild-type advanced breast cancer whose disease has progressed on or after a CDK4/6 inhibitor and an aromatase inhibitor.1 For patients with HR-positive/HER2-negative breast cancer who progress on existing therapies, treatment options remain limited, particularly for patients with PIK3CA wild-type tumors who are not eligible for currently approved PI3K-targeted therapies. As a result, there is a continued need for therapies capable of overcoming treatment resistance and extending disease control in this setting.2

The approval is supported by findings from the Phase III VIKTORIA-1 trial (NCT055001886), which assessed gedatolisib-based regimens in patients with endocrine-resistant disease. Patients were randomized to receive fulvestrant alone, palbociclib and fulvestrant, or the aforementioned doublet therapy with gedatolisib. The primary endpoint was progression-free survival (PFS) assessed by blinded independent central review comparing the triplet regimen to fulvestrant and the doublet regimen to fulvestrant.3

The combination of gedatolisib, palbociclib, and fulvestrant resulted in a median PFS of 9.3 months versus 2.0 months in the fulvestrant arm, demonstrated a statistically significant improvement in PFS (HR 0.24, 95% CI: 0.17, 0.35). Patients receiving doublet therapy had a median PFS of 7.4 months, showing an additional statistically significant improvement over fulvestrant monotherapy (HR, 0.33, 95% CI: 0.24, 0.48). Safety findings were generally manageable, mostly consisted of grade 3 neutropenia, stomatitis, rash, nausea, hyperglycemia, diarrhea, and vomiting in all three arms.3 The approval will provide a much-needed targeted treatment option for patients with HR+/HER2-/PIK3CA wild-type advanced breast cancer, offering meaningful improvements in disease control in a population with limited therapeutic alternatives.

References:

  1. Center for Drug Evaluation and Research. FDA approves gedatolisib with fulvestrant, with or without palbociclib, for HR-positive, HER2-negative locally advanced or metastatic breast cancer [Internet]. U.S. Food and Drug Administration. 2026 [cited 2026 Jul 15]. Available from: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-gedatolisib-fulvestrant-or-without-palbociclib-hr-positive-her2-negative-locally
  2. Cho Y-B, Park K-S. The effect and treatment of PIK3CA mutations in breast cancer: Current understanding and future directions. Medicina. 2025 Mar 17;61(3):518. doi:10.3390/medicina61030518
  3. Hurvitz SA, Layman RM, Curigliano G, André F, Cristofanilli M, Kim S-B, et al. Viktoria-1 trial of Gedatolisib plus fulvestrant with or without palbociclib in hormone receptor–positive/HER2−/PIK3CA wild-type advanced breast cancer. Journal of Clinical Oncology. 2026 Apr 20;44(12):1108–19. doi:10.1200/jco-25-02643