New Drug: Gedatolisib for ER+ Advanced Breast Cancer

This phase III randomized trial demonstrated that adding gedatolisib to fulvestrant, with or without palbociclib, significantly improved progression-free survival compared to fulvestrant alone in hormone receptor-positive, HER2-negative, PIK3CA wild-type advanced breast cancer patients previously treated with CDK4/6 inhibitors and aromatase inhibitors. Both gedatolisib-containing regimens had manageable safety profiles and showed trends toward improved overall survival in interim analysis. The study supports the potential of gedatolisib-based combinations as new standards of care in this setting.

Study

Phase III randomized, global, open-label, multicenter trial [VIKTORIA-1; NCT05501886]

Hormone receptor-positive, HER2-negative, PIK3CA wild-type advanced breast cancer with progression during or after CDK4/6 inhibitor and aromatase inhibitor treatment

Randomized 1:1:1 to gedatolisib plus palbociclib and fulvestrant (GPF) (n=131) vs gedatolisib plus fulvestrant (GF) (n=130) vs fulvestrant alone (F alone) (n=131)

Efficacy

Order:

ORR: 31.5% vs 28.3% vs 1.0% (GPF vs. GF vs. F alone)

mPFS: 9.3 mos vs 7.4 mos vs 2.0 mos

HR for progression or death: 0.24 [0.17-0.35] and 0.33 [0.24-0.48] for triplet and doublet vs fulvestrant

mOS (interim): 23.7 mos vs NR vs 18.5 mos

HR for death: 0.69 [0.43-1.12] and 0.74 [0.46-1.19] triplet and doublet vs fulvestrant

Safety

Grade >=3 TRAEs: neutropenia (52.3% vs 0% vs 0.8%), stomatitis (19.2% vs 12.3% vs 0%), rash (4.6% vs 5.4% vs 0%), nausea (3.8% vs 0.8% vs 0%), hyperglycemia (2.3% vs 2.3% vs 0%), diarrhea (1.5% vs 0.8% vs 0%), leukopenia (6.2% vs 0% vs 0%), thrombocytopenia (0.8% vs 0% vs 0.8%), pneumonitis (0% vs 0.8% vs 0%)

Treatment discontinuation due to TRAEs: 2.3% vs 3.1% vs 0%