VIKTORIA-1 Trial of Gedatolisib Plus Fulvestrant With or Without Palbociclib in Hormone Receptor-Positive/HER2-/PIK3CA Wild-Type Advanced Breast Cancer.
Journal
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
Journal Volume
44
Journal Issue
12
Start Page
Article number JCO-25-02643
ISSN
1527-7755
Date Issued
2026-04-20
Author(s)
Hurvitz, Sara A
Layman, Rachel M
Curigliano, Giuseppe
André, Fabrice
Cristofanilli, Massimo
Kim, Sung-Bae
Martínez Rodríguez, Jorge Luis
Nadal, Jorge C
Kim, Gun Min
Lo, Louisa
Remolina-Bonilla, Yuly A
Rosselli, Geronimo
Emile, George
Korbenfeld, Ernesto
Puig, Juan Manuel
Wesolowski, Robert
Martin, Miguel
Ring, Alistair
Han, Hyo S
Giordano, Antonio
Mutka, Sarah C
Moss, Keren
Suzuki, Sam
Sullivan, Brian
Gorbatchevsky, Igor
Et al.
Abstract
Gedatolisib potently targets all four class I PI3K isoforms and mTORC1 and mTORC2 to comprehensively block the PI3K/AKT/mTOR pathway and has shown compelling activity in early clinical trials with palbociclib and fulvestrant.
This phase III randomized trial (VIKTORIA-1; ClinicalTrials.gov identifier: NCT05501886) evaluated the efficacy of gedatolisib-based therapy, comparing gedatolisib, palbociclib, and fulvestrant (gedatolisib triplet) and gedatolisib plus fulvestrant (gedatolisib doublet) with fulvestrant monotherapy in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HER2-), wild-type (WT) advanced breast cancer. Eligible patients had disease progression during or after CDK4/6 inhibitor and aromatase inhibitor treatment. Comparison of progression-free survival as assessed by blinded independent central review for gedatolisib triplet versus fulvestrant and gedatolisib doublet versus fulvestrant was the primary objective.
A total of 392 patients were randomly assigned 1:1:1. The median study follow-up was 10.1 months. The median progression-free survival was 9.3 months in the gedatolisib-triplet group, 2.0 months in the fulvestrant group (hazard ratio [HR] for progression or death, 0.24 [95% CI, 0.17 to 0.35]; < .001), and 7.4 months in the gedatolisib-doublet group (HR, 0.33 [95% CI, 0.24 to 0.48]; < .001 fulvestrant). Grade ≥3 treatment-related adverse events (TRAEs) reported in the gedatolisib-triplet and gedatolisib-doublet groups, respectively, included neutropenia (62.3%, 0.8%), stomatitis (19.2%, 12.3%), rash (4.6%, 5.4%), hyperglycemia (2.3%, 2.3%), and diarrhea (1.5%, 0.8%). Study treatment discontinuation because of TRAEs was reported in 2.3% (triplet) and 3.1% (doublet) of patients.
The addition of gedatolisib to fulvestrant, with or without palbociclib, significantly reduced the risk of disease progression or death in patients with hormone receptor-positive/HER2-, WT advanced breast cancer.
Type
journal article