Loupakis, Fotios ORCID: 0000-0001-9651-0395, Yang, Dongyun ORCID: 0000-0003-0736-4977, Yau, Linda, Feng, Shibao, Cremolini, Chiara, Zhang, Wu, Maus, Martin K. H., Antoniotti, Carlotta, Langer, Christiane, Scherer, Stefan J., Mueller, Thomas, Hurwitz, Herbert I., Saltz, Leonard ORCID: 0000-0001-8353-4670, Falcone, Alfredo ORCID: 0000-0001-5840-2529 and Lenz, Heinz-Josef (2015). Primary Tumor Location as a Prognostic Factor in Metastatic Colorectal Cancer. JNCI-J. Natl. Cancer Inst., 107 (3). CARY: OXFORD UNIV PRESS INC. ISSN 1460-2105

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Abstract

Background: We sought to clarify the prognostic impact of primary tumor location in metastatic colorectal cancer (mCRC). Methods: We evaluated the association between tumor location and survival parameters in patients with previously untreated mCRC receiving first-line chemotherapy +/- bevacizumab in three independent cohorts: a prospective pharmacogenetic study (PROVETTA) and two randomized phase III trials, AVF2107g and NO16966. Cancers proximal or distal of the splenic flexure were classified as right-sided or left-sided, respectively. The primary end point was overall survival (OS). Data were analyzed with Cox proportional hazards and logistic regression models. All statistical tests were two-sided. Results: Among evaluable patients in the PROVETTA (n = 200), AVF2107g (n = 559), and NO16966 (n = 1268) studies, 72.0%, 63.1%, and 73.7% had left-sided tumors, respectively. In PROVETTA, patients with left-sided tumors had superior OS (left-sided vs right-sided: hazard ratio [HR] = .44, 95% confidence interval [CI] = .28 to .70, P < .001) and progression-free survival (HR = .52, 95% CI = .36 to .75, P < .001) outcomes. Multivariable analyses confirmed right-sided location as a negative prognostic variable, independent of mucinous histology and BRAF mutational status. Data from the AVF2107g (HR for OS = .55, 95% CI = .43 to.70) and NO16966 trials (HR for OS = .71, 95% CI = .62 to .82 both P < .001) also showed favorable outcomes in patients with left-sided tumors. In both randomized studies, the efficacy of bevacizumab was independent of tumor location. Conclusions: These data demonstrate that primary tumor location is an important prognostic factor in previously untreated mCRC. 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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Loupakis, FotiosUNSPECIFIEDorcid.org/0000-0001-9651-0395UNSPECIFIED
Yang, DongyunUNSPECIFIEDorcid.org/0000-0003-0736-4977UNSPECIFIED
Yau, LindaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Feng, ShibaoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cremolini, ChiaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zhang, WuUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Maus, Martin K. H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Antoniotti, CarlottaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Langer, ChristianeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Scherer, Stefan J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mueller, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hurwitz, Herbert I.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Saltz, LeonardUNSPECIFIEDorcid.org/0000-0001-8353-4670UNSPECIFIED
Falcone, AlfredoUNSPECIFIEDorcid.org/0000-0001-5840-2529UNSPECIFIED
Lenz, Heinz-JosefUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-406886
DOI: 10.1093/jnci/dju427
Journal or Publication Title: JNCI-J. Natl. Cancer Inst.
Volume: 107
Number: 3
Date: 2015
Publisher: OXFORD UNIV PRESS INC
Place of Publication: CARY
ISSN: 1460-2105
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
COLON-CANCER; 1ST-LINE THERAPY; SURVIVAL; BEVACIZUMAB; EPIDEMIOLOGY; EVOLUTION; PATTERNMultiple languages
OncologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/40688

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