Sara Hurvitz, MD, Fred Hutchinson Cancer Center, Seattle, Washington, discusses results from the phase 3 VIKTORIA-1 trial, which evaluated gedatolisib, a pan-PI3K/mTOR inhibitor, in combination with palbociclib and fulvestrant in patients with hormone receptor (HR)-positive, human epidermal growth factor receptor (HER2)-negative advanced breast cancer who experienced disease progression after first-line endocrine therapy with CDK4/6 inhibition.

The study findings, presented at the 2025 ESMO Congress, support gedatolisib combination therapy as a potential new standard of care for the second-line treatment for this patient population.

Transcript: 

Hi, I am Dr Sara Hurvitz, medical oncologist from the Fred Hutch Cancer Center, University of Washington, and I presented the results of the VIKTORIA-1 study. VIKTORIA-1 is a phase 3, open-label, randomized clinical trial that aimed to evaluate a novel PI3K/mTOR inhibitor, which is gedatolisib. Gedatolisib has been shown in a phase 1 study to be effective in patients with hormone receptor positive, HER2-negative metastatic breast cancer, regardless of PI3KCA mutation status. 

In VIKTORIA-1, we actually designed 2 studies. Study 1 was evaluating the use of gedatolisib in combination with fulvestrant and palbociclib, gedatolisib in combination with just fulvestrant, or fulvestrant alone in patients who had PI3KCA wild-type tumors. Patients were allowed to have up to 2 prior lines of endocrine therapy, no prior chemotherapy, and were randomized 1:1:1to these treatment arms.Progression-free survival was the primary end point, and it’s important to note that crossover in patients who were assigned to the fulvestrant arm was allowed. The study demonstrated that the triplet combination was significantly better than single-agent fulvestrant in terms of median progression-free survival, with a hazard ratio of 0.24. The median PFS of the triplet was 9.3 months and the median PFS of single-agent fulvestrant was 2 months.The doublet was also significantly better in terms of PFS compared to single-agent fulvestrant—7.4 months versus 2 months. The safety profile was interesting because unlike other PI3K pathway inhibitors, gedatolisib had a lower rate of diarrhea and hyperglycemia. Patients did experience stomatitis. Overall survival data were immature at the time of reporting—only 48% of events had been observed—but there was a strong trend in favor of both the triplet and the doublet when compared to fulvestrant. The objective response rates were also better in the triplet and doublet arms, as was the clinical benefit rate. 

In summary, this study demonstrated that the triplet combination of gedatolisib with fulvestrant and palbociclib and the doublet combination of fulvestrant with gedatolisib, were both significantly better than single-agent fulvestrant. All patients in this study had previously received a CDK4/6 inhibitor, and so these data are really quite striking. The safety and tolerability were also notable, and so we’re hoping that, in the future—not so long from now—we’ll have gedatolisib available for patients who have PI3KCA wild-type breast cancer.

Source: 

Hurvitz S, Layman RM, Curigliano G, et al. Gedatolisib (geda) + fulvestrant ± palbociclib (palbo) vs fulvestrant in patients (pts) with HR+/ HER2-/PIK3CA wild-type (WT) advanced breast cancer (ABC): First results from VIKTORIA-1. Presented at the 2025 ESMO Congress. October 17-21, 2025; Berlin, Germany. LBA17