Therapeutic Response Statement (Sensitivity)
This therapeutic response statement supports the relationship that HER2-positive, Wild type KRAS, Wild type NRAS status confers therapeutic sensitivity to Trastuzumab, Tucatinib in patients with Colorectal Adenocarcinoma.
The U.S. Food and Drug Administration granted accelerated approval to tucatinib in combination with trastuzumab for the treatment of adult patients with RAS wild-type HER2-positive unresectable or metastatic colorectal cancer that has progressed following treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy. The label notes that this indication is approved under accelerated approval based on tumor response rate and durability of response and that continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. This indication is based on MOUNTAINEER (NCT03043313), an open-label, multicenter trial where RAS status was performed as standard of care prior to study entry based on expanded RAS testing including KRAS exons 2, 3, and 4 and NRAS exons 2, 3, and 4.
This statement is based on a regulatory approval from the Food and Drug Administration:
TUKYSA is a kinase inhibitor indicated in combination with trastuzumab for the treatment of adult patients with RAS wild-type HER2-positive unresectable or metastatic colorectal cancer that has progressed following treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy. This indication is approved under accelerated approval based on tumor response rate and durability of response [see Clinical Studies (14.2)]. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.