Kirsten rat sarcoma (KRAS) oncogene mutation predicts magnitude of response and outcomes in hepatic arterial infusion pump therapy of unresectable colorectal liver metastases.

Abstract

The Kirsten rat sarcoma (KRAS) mutation predicts negative outcomes following resection of colorectal liver metastases (CRLM) and adjuvant hepatic arterial infusion (HAI) pump chemotherapy. Less is known on the effects of KRAS mutation on tumor response in patients with unresectable CRLM undergoing HAI chemotherapy with floxuridine. This is a retrospective cohort study investigating the effects of KRAS mutation on tumor response in patients with unresectable CRLM treated with HAI chemotherapy. Primary endpoint was objective response rate (ORR), secondary endpoints included overall tumor response and conversion to resectability. Twenty-five patients with unresectable liver metastases from colorectal cancer were treated with HAI chemotherapy between 2017-2019. Median number of liver lesions was 12 (range, 1-59) and almost all (n=24) had prior chemotherapy before starting HAI therapy. Median number of cycles administered via HAI pump was 6 (range, 3-12). Overall decrease in liver tumor burden was 63.5% (median; range, -257-100%) with an ORR of 20/25 (80%) and 10 (40%) patients converting to resectable status. Eleven (44%) patients had KRAS positive tumors. When compared to wild-type, KRAS positive tumors had less overall percent decrease (58% vs. 70%; P=0.04) and ORR (7/11 vs. 13/13; P=0.03). Fewer patients with KRAS positive tumors converted to resectable status during HAI therapy (2/11 vs. 8/13; P=0.05). At a median follow-up of 14.6 months (range, 4.0-36.6 months), overall survival is 45% among KRAS-positive and 77% for wild type patients. KRAS mutational status in patients with unresectable liver metastases from colorectal cancer predicts worse response to HAI chemotherapy compared to wild type.