Effect of Primary Tumor Location on Second-or Later-line Treatment Outcomes in Patients With RAS Wild-type Metastatic Colorectal Cancer and All Treatment Lines in Patients With RAS Mutations in Four Randomized Panitumumab Studies

The results from the retrospective analyses of data from 4 phase III randomized panitumumab trials showed a worse prognosis for patients with right-versus left-sided RAS wild-type metastatic colorectal cancer (mCRC) receiving second-line or greater therapy. Furthermore, the addition of panitumumab to standard treatment provided benefit to patients with left-sided RAS wild-type tumors. Further research is needed to define the optimal treatment of RAS mutant and right-sided RAS wild-type mCRC. Background: The primary tumor location has a prognostic impact in metastatic colorectal cancer (mCRC). We report the results from retrospective analyses assessing the effect of tumor location on prognosis and efficacy of second- and later-line panitumumab treatment in patients with RAS wild-type (WT) mCRC and on prognosis in all lines of treatment in patients with RAS mutant (MT) mCRC. Patients and Methods: RAS WT data (n=483) from 2 randomized phase III panitumumab trials (ClinicalTrials.gov identifiers, NCT00339183 and NCT00113763) were analyzed for treatment outcomes stratified by tumor location. The second analysis assessed the effect of tumor location in RAS MT patients (n=1205) from 4 panitumumab studies (ClinicalTrials.gov identifiers, NCT00364013, NCT00819780, NCT00339183, and NCT00113763). Primary tumors located in the cecumto transverse colon were coded as right-sided; those located from the splenic flexure to the rectum were coded as left-sided. Results: Of all patients, the tumor location was ascertained for 83% to 88%; 71% to 77% of patients had left-sided tumors. RAS WT patients with right-sided tumors did worse for all efficacy parameters compared with those with left-sided tumors. The patients with left-sided tumors had better outcomes with panitumumab than with the comparator treatment. Because of the low patient numbers, no conclusions could be drawn for right-sided mCRC. The prognostic effect of tumor location on survival was unclear for RASMT patients. Conclusion: These retrospective analyses have confirmed that RASWT right-sided mCRC is associated with a poor prognosis, regardless of the treatment. RASWT patients with left-sided tumors benefitted from the addition of panitumumab in second or later treatment lines. Further research is warranted to determine the optimum management of right-sided mCRC and RAS MT tumors. (C) 2018 The Authors. Published by Elsevier Inc.