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 ( 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 ( 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.
Source (journal)
Clinical colorectal cancer
17 :3 (2018) , p. 170-178
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Publications with a UAntwerp address
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Creation 08.10.2018
Last edited 15.11.2022
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