FDA grants accelerated approval to tucatinib with trastuzumab for colorectal cancer
FDA granted on January 19, 2023 accelerated approval to tucatinib (Tukysa, Seagen) in combination with trastuzumab (Herceptin, Genentech) for RAS wild-type HER2-positive unresectable or metastatic colorectal cancer that has progressed following fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy.
Approval was based on MOUNTAINEER (NCT03043313), an open-label, multicenter trial that evaluated efficacy in 84 patients. Patients were required to have HER2-positive, RAS wild-type, unresectable or metastatic colorectal cancer and prior treatment with fluoropyrimidine, oxaliplatin, irinotecan, and an anti-vascular endothelial growth factor (VEGF) monoclonal antibody (mAb). Patients whose tumors were deficient in mismatch repair (dMMR) proteins or were microsatellite instability-high (MSI-H) must also have received an anti-programmed cell death protein-1 mAb. Patients who received prior anti-HER2 targeting therapy were excluded.
Patients received tucatinib 300 mg orally twice daily with trastuzumab (or a non-U.S. approved trastuzumab product) administered at a loading dose of 8 mg/kg intravenously on Day 1 of Cycle 1 followed by a maintenance dose of trastuzumab 6 mg/kg on Day 1 of each subsequent 21-day cycle.
Patients were treated until disease progression or unacceptable toxicity.
The major efficacy measures were overall response rate (ORR) and duration of response (DOR) as assessed by blinded independent central review (RECIST version 1.1.). ORR was 38% (95% CI: 28, 49) and median DOR was 12.4 months (95% CI: 8.5, 20.5).
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