U veljačiry 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.
Bolesnici su primali tucatinib 300 mg peroralno dva puta dnevno zajedno s trastuzumabom (ili proizvodom trastuzumaba koji nije odobren za uporabu u Sjedinjenim Državama) davan u dozi punjenja od 8 mg/kg intravenozno 1. dana ciklusa 1 i dozom održavanja od 6 mg/ kg 1. dana svakog sljedećeg ciklusa od 21 dana. Pacijenti su primali liječenje sve do pojave neprihvatljivih nuspojava.
Ukupna stopa odgovora (ORR) i trajanje odgovora (DOR), kako je utvrđeno slijepim neovisnim središnjim pregledom, bile su ključne mjere učinkovitosti (RECIST verzija 1.1.). Medijan DOR-a bio je 12.4 mjeseca (95% CI: 8.5, 20.5), a ORR 38% (95% CI: 28, 49).
Proljev, letargija, osip, mučnina, nelagoda u trbuhu, reakcije povezane s infuzijom i pireksija bile su najčešće nuspojave (20%). Povišeni kreatinin, hiperglikemija, ALT, sniženi hemoglobin, AST, bilirubin, povećana alkalna fosfataza, sniženi limfociti, sniženi albumin, sniženi leukociti i sniženi natrij bile su najčešće laboratorijske abnormalnosti (20%).
U kombinaciji s trastuzumabom, savjetuje se doza od 300 mg tucatiniba oralno dva puta dnevno dok bolest ne napreduje ili dok ne dođe do neprihvatljive toksičnosti.
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.
