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

Joao Paulo Solar Vasconcelos, Nan Chen, Emma Titmuss, Dongsheng Tu, Stephanie Y. Brule, Rachel Goodwin, Derek J. Jonker, Timothy Price, John R. Zalcberg, Malcolm J. Moore, Christos S. Karapetis, Lillian Siu, Jeremy Shapiro, John Simes, Sharlene Gill, Chris J. O’Callaghan, Jonathan M. Loree

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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 colorectal cancer 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 wild-type (WT) mCRC from CO.17 and KRAS WT mCRC from CO.20 were analyzed according to location. Results: A total of 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% confidence interval (CI), 0.28–1.42; P¼0.26] and progression-free survival (PFS; median, 1.8 vs. 1.3 months; HR, 0.57; 95% CI, 0.26–1.28; P¼0.16). 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; P¼0.43) and PFS (median, 1.9 vs. 1.8 months; HR, 0.78; 95% CI, 0.49–1.26; P¼0.31). Patients with left-sided mCRC had superior outcomes with cetuximab compared with transverse for OS (median, 9.7 vs. 5.9 months; HR, 0.42; 95% CI, 0.27–0.67; P¼0.0002) and PFS (median, 3.8 vs. 1.8 months; HR, 0,49; 95% CI, 0.31–0.76; P¼0.001). Location was not prognostic in patients treated with BSC alone. Conclusions: Transverse mCRC has comparable prognostic and predictive features with right-sided mCRC.

Original languageEnglish
Pages (from-to)1121-1130
Number of pages10
JournalClinical Cancer Research
Volume30
Issue number6
DOIs
Publication statusPublished - 15 Mar 2024

Keywords

  • transverse colon
  • primary tumor
  • metastatic colorectal cancer
  • CCTG/AGITG CO.17
  • randomized clinical trials

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