Objective:

To evaluate the efficacy of gedatolisib in combination with fulvestrant, with or without palbociclib, in patients with hormone receptor-positive, HER2-negative breast cancer.

Approach:

• Study Design: An open-label, randomized, multicenter study (VIKTORIA-1 trial) enrolled 392 patients with locally advanced or metastatic hormone receptor-positive, HER2-negative breast cancer.
• Treatment Groups: Patients were assigned to receive gedatolisib with fulvestrant and palbociclib, gedatolisib with fulvestrant, or fulvestrant alone.
• Efficacy Measurement: Progression-free survival was assessed by blinded independent central review according to RECIST version 1.1.

Key Findings:

• Median progression-free survival was 9.3 months for gedatolisib, fulvestrant, and palbociclib versus 2.0 months for fulvestrant alone.
• Median progression-free survival was 7.4 months for gedatolisib and fulvestrant versus 2.0 months for fulvestrant alone.
• Objective response rates were 32% with the three-drug regimen, 28% with gedatolisib and fulvestrant, and 1% with fulvestrant alone.
• Median duration of response was 17.5 months with the three-drug regimen and 12.0 months with gedatolisib and fulvestrant.

Interpretation:

Overall survival data were not mature at the time of the progression-free survival analysis.

Limitations:

• The study did not provide mature overall survival data.
• Potential adverse reactions include stomatitis, dermatologic issues, hyperglycemia, and embryo-fetal toxicity.

Conclusion:

Gedatolisib has been approved for use in specific breast cancer patients following disease progression on endocrine therapy.

Sources:

• US Food and Drug Administration