Background: In the RAS wt population of APEC, q2w cetuximab combined with 1L FOLFOX or FOLFIRI achieved a best confirmed overall response rate (BORR), median progression-free survival (PFS), and median overall survival (OS) similar to those reported in prior 1L pivotal studies involving weekly (qw) cetuximab. In this hypothesis-generating subgroup analysis, we evaluated the impact of TS in APEC study patients with RAS wt mCRC. Methods: APEC was a nonrandomized phase 2 trial conducted in the Asia-Pacific region, with BORR as the primary endpoint. Patients with KRAS exon 2 wt tumors received q2w cetuximab + investigator’s choice of FOLFOX or FOLFIRI; subsequent analyses considered patients who were RAS wt (KRAS/NRAS, exons 2-4). TS 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 TS; 130 (81.8%) had L-sided and 29 (18.2%) had R-sided mCRC. Baseline characteristics in the TS subgroups reflected the known differences between L- and R-sided mCRC. Efficacy data for the TS subgroups are summarized in the table. Conclusions: Consistent with prior 1L pivotal studies involving qw cetuximab, a prognostic effect of TS in patients receiving 1L q2w cetuximab was confirmed in APEC. BORR remained ≥50% in patients with R-sided mCRC, in line with prior evidence that use of cetuximab may be appropriate when tumor shrinkage/cytoreduction is the goal. These hypothesis-generating data also raise the possibility of synergy between cetuximab and, in particular, irinotecan for PFS and OS in patients with R-sided tumors, although numbers are small. Clinical trial information: NCT00778830