Better Responses to Hepatic Arterial Infusion Therapy Among Patients With KRAS Wild-Type Metastatic Colorectal Cancer

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Patients with colorectal cancer and unresectable liver metastases and KRAS wild-type disease experienced better responses to hepatic arterial infusion pump chemotherapy than did patients with KRAS mutations, a retrospective cohort study found.

At a median follow-up of 14.6 months, “KRAS-positive patients had worse objective response rates at 64% vs 100% for wild-type patients,” Hordur M. Kolbeinsson, MD, a resident physician at Spectrum Health, College of Human Medicine, Michigan State University, Grand Rapids, reported at the Society of Surgical Oncology (SSO) 2021 International Conference on Surgical Cancer Care.1 “Overall median magnitude of response was 58% vs 70% for wild-type, and the rate of conversion to resectability was 18% with KRAS mutations, compared with 62% for wild-type patients.”

Gaining Momentum

Among the 30% to 50% of patients with colorectal cancer who develop metastases, “the liver is by far the most common site,” Dr. Kolbeinsson noted. “Hepatic arterial infusion chemotherapy has slowly been gaining momentum as a treatment modality for colorectal liver metastases, although utilization is mostly limited to a few specialized centers.” Previous studies have shown that the combination of modern systemic chemotherapy and hepatic arterial infusion chemotherapy improved survival over systemic chemotherapy alone, Dr. Kolbeinsson reported.

“KRAS-positive patients had worse objective response rates [to hepatic arterial infusion therapy] at 64% vs 100% for wild-type patients.”
— Hordur M. Kolbeinsson, MD

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“The KRAS oncogene mutation is associated with earlier systemic progression of colorectal cancer and worse prognosis,” Dr. Kolbeinsson said. Recent data have shown that patients with KRAS-mutated colorectal cancer and resectable liver metastases had worse overall survival compared with those who had wild-type status, although both groups benefited. The recent study looks at the effects of KRAS mutations in response to hepatic arterial infusion therapy in patients with unresectable colorectal liver metastases.

Stratified by Mutation Status

The single-institution retrospective cohort study included all patients with colorectal cancer and unresectable liver metastases treated with hepatic arterial infusion chemotherapy (floxuridine administered with dexamethasone) between August 2017 and September 2020. Of the 25 patients meeting inclusion criteria, 13 had wild-type status,11 had a KRAS mutation, and 1 had a BRAF mutation; the patient with the BRAF mutation was excluded from analysis.

The median age of the patients was 59 years, and 52% were men. The median number of liver lesions was 12 (range = 1–59 lesions).

All but 1 patient had prior systemic chemotherapy, and 10 patients had received 2 prior chemotherapy regimens. The median number of chemotherapy cycles was five for patients with KRAS mutations and four for those with wild-type status. The median number of cycles administered via hepatic arterial infusion pump was six for both groups. “Wild-type patients had a median shorter hospital stay while undergoing their hepatic arterial infusion pump placements,” Dr. Kolbeinsson noted. “Three patients had a percent increase in tumor burden, and all had a KRAS mutation.”

Patients With KRAS-Mutated Disease May Still Benefit

“Patients with kras-positive liver metastases had a worse objective response rate, overall magnitude of response, and lower rates of conversion to resectable disease compared with wild-type patients. This is hardly unexpected given what we know on the effects of KRAS mutations on overall outcomes in colorectal cancer,” Dr. Kolbeinsson said.

“Nevertheless, the objective response rate of KRAS-mutated patients in our cohort was 64%, which has to be considered a favorable response, given this was third-line treatment for 4 of the 11 patients in that group,” Dr. Kolbeinsson continued. “It seems clear that KRAS-mutated patients are still able to benefit from the treatment. In select patients, the response and conversion rates are still better than in second- and third-line systemic chemotherapy alone.” For these reasons, “KRAS mutational status alone should not guide patient selection for hepatic arterial infusion chemotherapy.”

“Study limitations include size and lack of survival data,” Dr. Kolbeinsson acknowledged. “Larger studies are needed to drive meaningful survival data. However, this will hopefully be possible soon with the help of a newly formed multi-institutional consortium.” In addition, “future studies should investigate the most appropriate timing of hepatic arterial infusion chemotherapy in the setting of unresectable colorectal liver metastases.” 

DISCLOSURE: Dr. Kolbeinsson reported no conflicts of interest.


1. Preihs R, Bengel A, Assifi M, et al: KRAS mutation predicts magnitude of response and outcomes in hepatic arterial infusion pump therapy of unresectable colorectal liver metastases. SSO 2021 International Conference on Surgical Care. Abstract 39. Presented March 18, 2021.