VIKTORIA-1: PAM inhibition efficacious in HR+ HER2- PIK3CA wild-type aBC

Second-line gedatolisib plus fulvestrant, with or without palbociclib, demonstrated superior efficacy compared with fulvestrant monotherapy in patients with PIK3CA wild-type, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (aBC). Gedatolisib-based therapy was generally well tolerated, supporting its potential use in the study population.

In the VIKTORIA-1 study (NCT05501886), 392 participants with HR-positive, HER2-negative aBC and PIK3CA wild-type disease, who had previously received a CDK4/6 inhibitor and a non-steroidal aromatase inhibitor, were randomised 1:1:1 to receive the PI3K-AKT-mTOR (PAM) inhibitor gedatolisib plus fulvestrant with or without palbociclib, or fulvestrant alone. The primary endpoints were progression-free survival (PFS) assessed by blinded independent central review (BICR) for the gedatolisib-containing arms (A and B) versus the monotherapy arm (C).

After a median follow-up of 10.1 months, gedatolisib triplet therapy significantly improved median PFS as compared with fulvestrant alone (9.3 vs 2.0 months; adjusted HR 0.24; 95% CI 0.17-0.35; P<0.0001). Gedatolisib doublet therapy also outperformed fulvestrant monotherapy in terms of median PFS (7.4 vs 2.0 months; adjusted HR 0.33; 95% CI 0.24-0.48; P<0.0001). “The triplet therapy may be more efficacious than the doublet therapy in pre-/perimenopausal patients, in patients with visceral metastases, and in those who received palbociclib as their prior CDK4/6 inhibitor,” said Dr Sara Hurvitz (Fred Hutchinson Cancer Center, WA, USA) when discussing the PFS subgroup comparison between arms A and B [1].

The serious adverse event rates were 10.8%, 9.2%, and 0.8% for triplet, doublet, and monotherapy arms, respectively. Grade 3 stomatitis (19.2% vs 12.3% vs 0%), rash (4.6% vs 5.4% vs 0%), diarrhoea (1.5% vs 0.8% vs 0%), and hyperglycaemia (2.3% vs 2.3% vs 0%) were more frequently observed in the gedatolisib-containing regimens than with fulvestrant.

“These findings validate the PAM pathway as a molecular driver in PIK3CA wild-type disease and show that gedatolisib plus fulvestrant, with or without palbociclib, is a promising standard-of-care candidate for the second-line treatment in patients with HR-positive, HER2-negative, PIK3CA wild-type aBC,” concluded Dr Hurvitz.

1. Hurvitz SA, et al. Gedatolisib plus fulvestrant, with & without palbociclib, vs fulvestrant in patients with HR+/HER2-/PIK3CA wild-type advanced breast cancer: first results from VIKTORIA-1. LBA17. European Society for Medical Oncology (ESMO) Congress, 17-21 October 2025, Berlin, Germany.

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Posted on 15 December 20257 January 2026