Transverse Colon Primary Tumor Location as a Biomarker in Metastatic Colorectal Cancer: A Pooled Analysis of CCTG/AGITG CO.17 and CO.20 Randomized Clinical Trials

Abstract

Purpose: Sidedness is prognostic and predictive of anti-EGFR efficacy in metastatic colorectal cancer (mCRC). Transverse colon has been historically excluded from several analyses of sidedness and the optimal division between left and right-sided CRC is unclear. We investigated transverse colon primary tumor location as a biomarker in mCRC. Experimental Design: Pooled analysis of CCTG/AGITG CO.17 and CO.20 trials of cetuximab in chemotherapy-refractory mCRC. Outcomes of patients with RAS/BRAF wildtype mCRC from CO.17 and KRAS wildtype mCRC from CO.20 were analyzed according to location. Results: 553 patients were analyzed, 32 (5.8%) with cancers from the transverse, 101 (18.3%) from right, and 420 from (75.9%) left colon. Transverse mCRC failed to reach significant benefit from cetuximab versus best supportive care (BSC) for overall Survival (OS) (median, 5.9 vs. 2.1 months; HR, 0.63; 95% CI, 0.28–1.42; P=0.26) and progression-free survival (PFS) (median, 1.8 vs. 1.3 months; HR, 0.57; 95% CI, 0.26–1.28; P=0.16). Analyzing exclusively patients randomized to cetuximab, right-sided and transverse had comparable outcomes for OS (median, 5.6 vs. 5.9 months; HR, 0.82; 95% CI, 0.50–1.34; P=0.43) and PFS (median, 1.9 vs. 1.8 months; HR, 0.78; 95% CI, 0.49–1.26; P=0.31). Patients with left-sided mCRC had superior outcomes with cetuximab compared to transverse for OS (median, 9.7 vs. 5.9 months; HR, 0.42; 95% CI, 0.27–0.67; P=0.0002) and PFS (median, 3.8 vs. 1.8 months; HR, 0,49; 95% CI, 0.31–0.76; P=0.001). Location was not prognostic in patients treated with BSC alone. Conclusion: Transverse mCRC has comparable prognostic and predictive features to right-sided mCRC.