Left-Sided Primary Tumor Location More Common and Associated With Better Survival in Metastatic Colorectal Cancer


Key Points

  • Left-sided primary tumor location was associated with improved overall survival independent of mucinous histology and BRAF mutation status in most treatment-naive patients with metastatic colorectal cancer.
  • Stratification for left- vs right-sided location should be considered in clinical trials.

In a study reported in the Journal of the National Cancer Institute, Loupakis et al found that most treatment-naive patients with metastatic colorectal cancer had left-sided primary tumor location and that left-sided tumor location was associated with improved overall survival.

Study Details

The study involved data from patients with previously untreated metastatic colorectal cancer receiving first-line treatment with or without bevacizumab (Avastin) in the PROVETTA pharmacogenetic study (N = 200) and the phase III AVF2107g (N = 559) and NO16966 (N = 1,268) trials. Cancers proximal to vs distal from the splenic flexure were classified as right-sided vs left-sided. Multivariate analyses adjusted for age, gender, race, Kohne score, and prior adjuvant chemotherapy; analysis in the PROVETTA population also adjusted for BRAF mutation status and mucinous histology.

Improved Overall Survival

In PROVETTA, AVF2107g, and NO16966, primary tumors were left-sided in 72.0%, 63.1%, and 73.7%, respectively. In PROVETTA, right-sided tumors were more frequently BRAF-mutated (P < .001), with the association remaining significant after adjustment for mucinous histology (P = .001). Patients with left-sided tumors had better overall survival (hazard ratio [HR] = 0.44, P < .001) and progression-free survival (HR = 0.52, P < .001). On multivariate analyses, left-sided location was associated with significantly better overall survival among all patients (HR = 0.47, P = .01) and among 155 with BRAF wild-type and nonmucinous disease (HR = 0.47, P = .02).

Overall survival was significantly better with left-sided tumor location in both AVF2107g (HR = 0.55, P < .001) and NO16966 (HR = 0.71, P < .001), with significance maintained on multivariate analysis (HR = 0.52, P < .001; HR = 0.72, P < .001). In both AVF2107g (HR = 0.71, P = .01) and NO16966 (HR = 0.82, P = .01), overall survival was better with bevacizumab treatment independent of primary tumor location.

The investigators concluded: “These data demonstrate that primary tumor location is an important prognostic factor in previously untreated [metastatic colorectal cancer]. Given the consistency across an exploratory set and two confirmatory phase III studies, side of tumor origin should be considered for stratification in randomized trials.”

Heinz-Josef Lenz, MD, of University of Southern California Norris Comprehensive Cancer Center, is the corresponding author of the Journal of the National Cancer Institute article.

The work was supported by the National Institutes of Health, Daniel Butler Research Fund, ARCO Foundation, Genentech, and F. Hoffmann-La Roche. For full disclosures of the study authors, visit

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