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.
In a Swedish population-based screening cohort, the blood-based risk model had higher short-term sensitivity for clinically significant prostate cancer than prostate-specific antigen testing, with similar specificity.
