VIKTORIA-1: Updated results of a randomized, open-label, phase 3 study of gedatolisib (geda) + fulvestrant (fulv) ± palbociclib (palbo) vs standard of care in patients (pts) with HR+/HER2-advanced breast cancer (ABC) (Study 2)

VIKTORIA-1

Patient / Population Intervention / Exposure Comparison Outcome

In patients with HR+/HER2- PIK3CA-mutant advanced breast cancer, gedatolisib plus palbociclib and fulvestrant improved median progression-free survival compared with alpelisib plus fulvestrant.

N

—patients

Design

Randomised 3:3:1, open-label, phase 3 study (Study 2, PIK3CA mutant) in patients with HR+/HER2- advanced breast cancer comparing gedatolisib plus palbociclib plus fulvestrant (Arm D, n=155), alpelisib plus fulvestrant (Arm E, n=155) and gedatolisib plus fulvestrant (Arm F, n=52), all in 28-day cycles (NCT05501886).

Endpoint

Median progression-free survival with gedatolisib plus palbociclib plus fulvestrant vs alpelisib plus fulvestrant.

ResultPrimary endpoint met: gedatolisib plus palbociclib plus fulvestrant significantly improved median PFS vs alpelisib plus fulvestrant. The overall figures and P value are not given in the abstract. Arm D vs Arm E: with visceral metastases 9.8 vs 5.6 months (HR 0.52, 95% CI 0.37-0.74); without visceral metastases 21.5 vs 9.2 months (HR 0.38, 95% CI 0.19-0.82); with liver metastases 9.1 vs 4.6 months (HR 0.47, 95% CI 0.31-0.70); without liver metastases 21.5 vs 9.1 months (HR 0.46, 95% CI 0.28-0.78). Arm F vs Arm E: with visceral metastases 11.3 vs 5.6 months (HR 0.53, 95% CI 0.33-0.85); without visceral metastases not reached vs 9.2 months (HR 0.40, 95% CI 0.13-1.31); with liver metastases 11.1 vs 4.6 months (HR 0.38, 95% CI 0.20-0.69); without liver metastases 11.5 vs 9.1 months (HR 0.71, 95% CI 0.37-1.39). Median duration of response, including unconfirmed PR, was 19.4 months (95% CI 11.1-25.1) in Arm D, 27.8 months (95% CI 9.2-NE) in Arm F and 7.5 months (95% CI 5.6-16.6) in Arm E. TEAEs led to gedatolisib withdrawal in 8 patients (5.2%) in Arm D and 2 patients (3.8%) in Arm F. Grade 3 stomatitis beyond cycle 2 was <3%. Gedatolisib regimens had no clinically meaningful impact on fasting or non-fasting glucose.

Pistilli B, Curigliano G, André F, et al. Presented at ESMO Congress 2026, abstract LBA16, 24 October. Not yet published.

Discussion & critique

The update reports a consistent progression-free survival benefit for gedatolisib-containing regimens over alpelisib plus fulvestrant across subgroups defined by visceral and liver metastases, with longer responses and few discontinuations. The abstract does not report the overall primary endpoint figures, the P value, follow-up duration or any overall survival data, and the subgroup analyses were not shown to be powered. The gedatolisib plus fulvestrant arm is small, two of its four subgroup confidence intervals cross 1, and duration of response includes unconfirmed partial responses. The trial is open label with a progression-based endpoint and is funded by Celcuity, which also employs several of the authors.