Background: KRAS mutation is an established biomarker for lack of response to antiepidermal growth factor receptor (EGFR) antibodies in mCRC. We used next‑generation sequencing to investigate whether mutation of other genes known to be altered in CRC predict response to panitumumab. Methods: Banked formalin fixed paraffin‑embedded patient tumor samples from a randomized, phase III monotherapy clinical trial that compared panitumumab + best supportive care (BSC) with BSC alone (the 408 study) were sequenced. After disease progression, patients randomized to the BSC alone arm could enroll in an optional panitumumab extension study (the 194 study). Tumor samples previously analyzed for KRAS codon 12 and 13 mutations were sequenced for mutations in 9 genes: AKT1, BRAF, CTNNB1, EGFR, KRAS (codon 61), NRAS, PIK3CA, PTEN, and TP53. This analysis presents pooled efficacy data from the 408 and 194 studies by genotype. Results: In the 408 study (multimarker data presented at AACR 2010), 463 patients were randomized to panitumumab + BSC (n = 231) or BSC alone (n = 232); 176 of these BSC alone patients enrolled in the 194 study. In total, 288 patients had multimarker data available; 257 of these were treated with panitumumab monotherapy on either study (147 from study 408 and 110 from study 194). In this treated population, 22/138 (15.9%) patients with wild type (WT) KRAS tumors compared with 0/103 (0%) with mutant (MT) KRAS (codons 12, 13) tumors had an objective response (OR). OR rates (ORR) for other single genotypes within the KRAS WT subset are shown (Table). Conclusions: Implications of tumor genotype at the 9 loci for clinical outcomes (ORR and progression‑free survival) with panitumumab and detailed results from the aggregate analysis of the 408 and 194 studies will be presented.