Dr Hurvitz on Data With Gedatolisib-Based Regimens in PIK3CA Wild-Type HR+/HER2-Negative Breast Cancer

"These data were impressive, even for patients with very endocrine-resistant breast cancer, where the triplet seemed particularly [effective]."

Sara A. Hurvitz, MD, FACP, a medical oncologist, senior vice president, director of and a professor in the Clinical Research Division, the Smith Family Endowed Chair in Women’s Health, and an affiliate investigator in the Translational Science and Therapeutics Division at Fred Hutchinson Cancer Center; as well as a professor in and head of the Division of Hematology and Oncology in the Department of Medicine at the University of Washington, expanded on efficacy and safety findings from the phase 3 VIKTORIA-1 study (NCT05501886) evaluating gedatolisib (PF-05212384) plus fulvestrant (Faslodex) with or without palbociclib (Ibrance) in patients with PIK3CA wild-type, hormone receptor–positive, HER2-negative metastatic breast cancer.

VIKTORIA-1 evaluated the benefit of incorporating the PI3K/mTOR inhibitor gedatolisib with standard endocrine therapy components. At the 2025 ESMO Congress, findings from VIKTORIA-1 were presented and demonstrated a statistically significant improvement in progression-free survival (PFS) using a triplet combination of gedatolisib plus palbociclib and fulvestrant, as well as a doublet combination of gedatolisib plus fulvestrant, vs fulvestrant alone.

Patients treated with the triplet regimen (n = 131) achieved a median PFS of 9.3 months (95% CI, 7.2-16.6). This result represented a substantial advantage over patients who received fulvestrant monotherapy (n = 131), whose median PFS was 2.0 months (95% CI, 1.8-2.3). The high efficacy of the triplet was reflected in the HR of 0.24 (95% CI, 0.17-0.35; P < .0001). Hurvitz highlighted that the impressive data were particularly notable for patients diagnosed with very endocrine-resistant breast cancer. The doublet arm (n = 130) also yielded significant benefit, with a median PFS of 7.4 months (95% CI, 5.5-9.9) vs fulvestrant alone (HR, 0.33; 95% CI, 0.24-0.48; P < .0001).

When considering safety, Hurvitz mentioned that typical on-target toxicities of PI3K pathway inhibitors include hyperglycemia and diarrhea. The VIKTORIA-1 study notably reported lower rates of these toxicities compared with those observed with other PI3K pathway inhibitors. However, Hurvitz emphasized that patients still had a risk of stomatitis, despite the preventative use of oral steroid mouthwash, requiring physicians to monitor this adverse effect closely when administering the therapy.