Phase II study of trastuzumab-pkrb plus gedatolisib in patients with HER2-positive metastatic breast cancer who progressed after two or more HER2-directed therapies
Targeting a dual pathway escape mechanism in advanced breast cancer produced responses in 43% of heavily pretreated patients with specific mutations.
This multicenter Korean Phase II study tested dual HER2/PI3K pathway blockade in 44 patients with HER2+ metastatic breast cancer harboring PIK3CA kinase domain mutations (59%), helical domain mutations (25%), or PTEN deletions (5%) who had progressed on at least two prior HER2-directed therapies. A 43.2% response rate and 24.74-month median overall survival support targeting PI3K pathway escape mechanisms, with ctDNA clearance emerging as a predictive biomarker of response.
What the study was
- Study design
- prospective_multicenter_phase2_single_arm
- Category
- novel_therapeutics
- Maturity
- Potentially Practice-Changing
- Journal
- ESMO Open
Why it surfaced
Prospective Phase II demonstrating 43% ORR with HER2/PI3K dual blockade in heavily pretreated population; addresses critical unmet need of HER2+ MBC progression after T-DM1 and T-DXd; ctDNA dynamics validated as response predictor.
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