V februarjury 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.
Bolniki so prejemali tukatinib v odmerku 300 mg peroralno dvakrat na dan skupaj s trastuzumabom (ali izdelkom s trastuzumabom, ki ni bil odobren za uporabo v Združenih državah), danim v polnilnem odmerku 8 mg/kg intravensko 1. dan 1. cikla in vzdrževalni odmerek 6 mg/kg. kg 1. dan vsakega naslednjega 21-dnevnega ciklusa. Bolniki so prejemali zdravljenje do pojava nesprejemljivih stranskih učinkov.
Stopnja splošnega odziva (ORR) in trajanje odziva (DOR), kot sta bila določena s slepim neodvisnim osrednjim pregledom, sta bila ključna merila učinkovitosti (RECIST različica 1.1.). Mediana DOR je bila 12.4 meseca (95 % IZ: 8.5, 20.5), ORR pa 38 % (95 % IZ: 28, 49).
Driska, letargija, izpuščaj, slabost, nelagodje v trebuhu, odzivi, povezani z infuzijo, in zvišana telesna temperatura so bili najpogostejši neželeni učinki (20 %). Zvišan kreatinin, hiperglikemija, ALT, znižan hemoglobin, AST, bilirubin, zvišana alkalna fosfataza, znižani limfociti, znižan albumin, znižan levkocit in znižan natrij so bile najpogostejše laboratorijske nenormalnosti (20 %).
V povezavi s trastuzumabom se priporoča odmerek 300 mg tukatiniba peroralno dvakrat na dan, dokler bolezen ne napreduje ali se pojavi nesprejemljiva toksičnost.
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.
