Artigo

VIKTORIA-1 Trial of Gedatolisib Plus Fulvestrant With orWithout Palbociclib in Hormone Receptor–Positive/HER22/PIK3CA Wild-Type Advanced Breast Cancer

Autor(es): Sara A. Hurvitz, MD 1 Sung-Bae Kim, MD, PhD 7 ; Rachel M. Layman, MD 2 ; Giuseppe Curigliano, MD, PhD 3,4 ; Jorge Luis Mart´ ınez Rodr´ ıguez, MD 8 ; Fabrice Andr´ e,MD, PhD 5 ; Jorge C. Nadal, MD 9 ; Massimo Cristofanilli, MD 6 ; Gun Min Kim, MD 10 ; ; Louisa Lo, MD, PhD 11 ; Yuly A. Remolina-Bonilla, MD 12 Robert Wesolowski, MD 17 ; Geronimo Rosselli, MD 13 ; Miguel Martin, MD, PhD 18 ; George Emile, MD 14 ; Alistair Ring, MD 19 ; Ernesto Korbenfeld, MD 15 ; Juan Manuel Puig, MD 16 ; ; Hyo S. Han, MD 20 ; Antonio Giordano, MD, PhD 21 Sarah C. Mutka, PhD 22 for the VIKTORIA-1 Study Group

ABSTRACT

PURPOSE 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.
METHODS 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 (HER22), PIK3CA wild-type (WT) advanced breast cancer. Eligible patients had disease progression during or after CDK4/6 inhibitor and aro matase 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.
RESULTS 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]; P < .001), and 7.4 months in the gedatolisib-doublet group (HR, 0.33 [95% CI, 0.24 to 0.48];
P < .001 v fulvestrant). Grade ≥3 treatment-related adverse events (TRAEs) reported in the gedatolisib-triplet and gedatolisib-doublet groups, respec tively, 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.
CONCLUSION The addition of gedatolisib to fulvestrant, with or without palbociclib, signif
icantly reduced the risk of disease progression or death in patients with hor
mone receptor–positive/HER22, PIK3CA WT advanced breast cancer.