I februarry 2023, the Food and Drug Administration (FDA) sped up the approval of tucatinib (Tukysa, Seagen Inc.) and trastuzumab for the treatment of RAS wild-type HER2-positive colorectal cancer that has spread or can not be removed after fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy.
An open-label, multicenter experiment called MOUNTAINEER (NCT03043313) examined effectiveness in 84 patients. Patients needed to have previously received treatment with fluoropyrimidine, oxaliplatin, irinotecan, and an anti-vascular endothelial growth factor (VEGF) monoclonal antibody in addition to having HER2-positive, RAS wild-type, unresectable, or metastatic colorectal cancer (mAb). People who needed an anti-programmed cell death protein-1 mAb also had cancers that did not have mismatch repair (dMMR) proteins or had a lot of microsatellite instability (MSI-H). Patients who had previously received anti-HER2 targeted therapy were not eligible.
Patienterne fik tucatinib 300 mg oralt to gange dagligt sammen med trastuzumab (eller et trastuzumab-produkt, der ikke er godkendt til brug i USA) givet i en ladningsdosis på 8 mg/kg intravenøst på dag 1 i cyklus 1 og en vedligeholdelsesdosis på 6 mg/ kg på dag 1 i hver efterfølgende 21-dages cyklus. Patienterne modtog behandling, indtil uacceptable bivirkninger opstod.
Samlet responsrate (ORR) og varighed af respons (DOR), som bestemt af en blindet uafhængig central gennemgang, var de vigtigste effektmål (RECIST version 1.1.). Median DOR var 12.4 måneder (95 % CI: 8.5, 20.5), og ORR var 38 % (95 % CI: 28, 49).
Diarré, sløvhed, udslæt, kvalme, ubehag i maven, infusionsrelaterede reaktioner og pyreksi var de hyppigste bivirkninger (20%). Øget kreatinin, hyperglykæmi, ALT, nedsat hæmoglobin, AST, bilirubin, øget alkalisk fosfatase, nedsat lymfocytter, nedsat albumin, nedsat leukocyttal og nedsat natrium var de mest udbredte laboratorieabnormiteter (20%).
I forbindelse med trastuzumab anbefales en dosis på 300 mg tucatinib oralt to gange dagligt, indtil sygdommen skrider frem, eller der er uacceptabel toksicitet.
Project Orbis, an initiative of the FDA Oncology Center of Excellence, was used to carry out this review. Using the infrastructure that Project Orbis provides, international partners can submit and review oncology medications simultaneously. The FDA and the Australian Therapeutic Goods Administration worked together on this review (TGA). At the other regulatory organisation, the application review is still proceeding.
