Tumor KRAS status predicts responsiveness to panitumumab in Japanese patients with metastatic colorectal cancer.

OBJECTIVE Mutation status of the KRAS gene in tumors has been shown to be a predictive biomarker of response to anti-epidermal growth factor receptor antibody therapy in patients with metastatic colorectal cancer. This retrospective analysis examined the association between efficacy and safety of the fully human anti-epidermal growth factor receptor antibody panitumumab and KRAS mutation status in Japanese metastatic colorectal cancer patients using data from two clinical trials with adherence to good clinical practices. METHODS An exploratory, integrated analysis of data from KRAS evaluable patients enrolled in a Phase 1 study (Study 20040192) and a Phase 2 study (Study 20050216) was performed. Paraffin-embedded tumor samples were analyzed for KRAS status. Primary efficacy endpoint of this analysis was objective tumor response per modified response evaluation criteria in solid tumors; a key secondary endpoint was progression-free survival. Safety endpoints included incidence of adverse events. RESULTS Tumor samples with known KRAS status were available from 8 of 13 (62%) metastatic colorectal cancer patients in the Phase 1 study and 16 of 53 patients (30%) in the Phase 2 study. Overall, 14 (58%) patients had wild-type KRAS tumors and 10 (42%) patients had mutated KRAS tumors. Four (17%) patients had a partial response; all responders had tumors with wild-type KRAS. Results of all secondary efficacy endpoints also favored patients with wild-type KRAS. Treatment-related adverse events were predominantly mild to moderate and skin related, and were similar between patients with tumors with wild-type and mutated KRAS in this small patient population. CONCLUSIONS Mutated KRAS status in tumors of Japanese patients with metastatic colorectal cancer is associated with lack of response to panitumumab therapy.