Background: In the RAS wt population of APEC, q2w cetuximab combined with first-line FOLFOX or FOLFIRI achieved an overall response rate (ORR), median progression-free survival (PFS), and median overall survival (OS) similar to those reported in prior first-line pivotal studies involving weekly cetuximab. In this subgroup analysis, we evaluated the impact of tumor side in the APEC study population with RAS wt mCRC. Methods: APEC was a nonrandomized phase 2 trial conducted in the Asia-Pacific region, with ORR as the primary endpoint. Patients with KRAS exon 2 wt tumors received q2w cetuximab + investigator’s choice of FOLFOX or FOLFIRI. Tumor side was categorized in evaluable patients with RAS wt tumors (left [L]-sided = splenic flexure, descending colon, sigmoid colon, and rectum; right [R]-sided = appendix, cecum, ascending colon, hepatic flexure, and transverse colon). Results: Among 167 patients with RAS wt mCRC, 159 were evaluable for tumor side; 130 (81.8%) had L-sided and 29 (18.2%) had R-sided mCRC. Baseline characteristics in the tumor side subgroups reflected the known differences between L- and R-sided mCRC; indeed, 95.4% and 75.9% of patients had BRAF wt disease, respectively. Efficacy data are summarized in the Table. Conclusions: Consistent with prior first-line pivotal studies with weekly cetuximab, a prognostic effect of tumor side in patients receiving first-line q2w cetuximab was confirmed in APEC. In patients with R-sided mCRC, ORR remained ≥ 50%, and resection rate was comparable to that of L-sided patients, in line with prior evidence showing that use of cetuximab may be appropriate when rapid tumor shrinkage is the goal. These hypothesis-generating data raise the possibility of a synergy between cetuximab and irinotecan in patients with R-sided tumors, although numbers are small. Clinical trial information: NCT00778830