Universität zu Köln

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:	Creators Email ORCID ORCID Put Code Loupakis, Fotios UNSPECIFIED orcid.org/0000-0001-9651-0395 UNSPECIFIED Yang, Dongyun UNSPECIFIED orcid.org/0000-0003-0736-4977 UNSPECIFIED Yau, Linda UNSPECIFIED UNSPECIFIED UNSPECIFIED Feng, Shibao UNSPECIFIED UNSPECIFIED UNSPECIFIED Cremolini, Chiara UNSPECIFIED UNSPECIFIED UNSPECIFIED Zhang, Wu UNSPECIFIED UNSPECIFIED UNSPECIFIED Maus, Martin K. H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Antoniotti, Carlotta UNSPECIFIED UNSPECIFIED UNSPECIFIED Langer, Christiane UNSPECIFIED UNSPECIFIED UNSPECIFIED Scherer, Stefan J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Mueller, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Hurwitz, Herbert I. UNSPECIFIED UNSPECIFIED UNSPECIFIED Saltz, Leonard UNSPECIFIED orcid.org/0000-0001-8353-4670 UNSPECIFIED Falcone, Alfredo UNSPECIFIED orcid.org/0000-0001-5840-2529 UNSPECIFIED Lenz, Heinz-Josef UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-411778
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:	Keywords Language COLON-CANCER; 1ST-LINE THERAPY; SURVIVAL; BEVACIZUMAB; EPIDEMIOLOGY; EVOLUTION; PATTERN Multiple languages Oncology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/41177