OBJECTIVES:  To conduct a systematic review to compare the efficacy and safety of panitumumab in patients of metastatic colorectal cancer (mCRC) by tumor KRAS status. METHODS:  Searches were performed on MEDLINE® from January 2000 to June 2016 and included all randomized controlled trials comparing panitumumab therapy in patients with wild type (WT) and mutant type (MT) mCRC. A systematic review approach was followed and qualitative analysis of the results was done. RESULTS: From the searches retrieved, two studies reached the stage of data extraction. First study evaluated panitumumab plus fluorouracil, leucovorin, and irinotecan (FOLFIRI) versus FOLFIRI alone after failure of initial treatment in 1186 patients and the second study compared panitumumab plus infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) with FOLFOX4 alone in 1183 patients with previously untreated mCRC. In the first study, a significant improvement in PFS was observed in WT-subpopulation after adding panitumumab to chemotherapy; median PFS was 5.9 months for panitumumab-FOLFIRI versus 3.9 months for FOLFIRI. A non-significant trend toward increased OS was observed; median OS was 14.5 versus 12.5 months, respectively; response rate was improved to 35% versus 10%. No difference in efficacy was seen in MT-KRAS patients. In the second study, a significant improvement in PFS was observed with panitumumab-FOLFOX4 compared with FOLFOX4 in WT-KRAS patients (median PFS, 9.6 versus 8.0 months, respectively). A non-significant increase in OS was observed for panitumumab-FOLFOX4 versus FOLFOX4 (median OS, 23.9 versus 19.7 months, respectively). In MT-KRAS patients, PFS was significantly reduced in panitumumab-FOLFOX4 arm versus FOLFOX4 arm, and median OS was 15.5 versus 19.3 months, respectively. Adverse event rates in both studies were generally comparable across arms with the exception of known toxicities associated with anti-EGFR therapy. CONCLUSIONS:  Panitumumab plus FOLFIRI or FOLFOX4 significantly improved PFS and is well-tolerated as second-line treatment in WT-KRAS mCRC than in MT-KRAS mCRC patients.