I februariry 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.
Patienterna fick tucatinib 300 mg oralt två gånger dagligen tillsammans med trastuzumab (eller en trastuzumab-produkt som inte är licensierad för användning i USA) givet i en laddningsdos på 8 mg/kg intravenöst på dag 1 av cykel 1 och en underhållsdos på 6 mg/ kg på dag 1 i varje efterföljande 21-dagarscykel. Patienterna fick behandling fram till början av oacceptabla biverkningar.
Övergripande svarsfrekvens (ORR) och duration of response (DOR), som fastställts av en blindad oberoende central granskning, var de viktigaste effektmåtten (RECIST version 1.1.). Median DOR var 12.4 månader (95 % KI: 8.5, 20.5) och ORR var 38 % (95 % KI: 28, 49).
Diarré, letargi, hudutslag, illamående, bukbesvär, infusionsrelaterade svar och pyrexi var de vanligaste biverkningarna (20%). Ökat kreatinin, hyperglykemi, ALAT, minskat hemoglobin, ASAT, bilirubin, ökat alkaliskt fosfatas, minskat antal lymfocyter, minskat albumin, minskat antal leukocyter och minskat natrium var de vanligaste laboratorieavvikelserna (20%).
I samband med trastuzumab rekommenderas en dos på 300 mg tucatinib oralt två gånger dagligen tills sjukdomen fortskrider eller det finns oacceptabel toxicitet.
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.
