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Ann Oncol. 2017 Aug 1;28(8):1862-1868. doi: 10.1093/annonc/mdx119.

Primary tumor sidedness has an impact on prognosis and treatment outcome in metastatic colorectal cancer: results from two randomized first-line panitumumab studies.

Author information

1
Center for Oncological Research (CORE), University of Antwerp, Wilrijk, Belgium.
2
Center of Medical Genetics, University of Antwerp and Antwerp University Hospital, Antwerp, Belgium.
3
Biostatistics, Amgen Ltd, Uxbridge, UK.
4
Department of Oncology, Antwerp University Hospital, Edegem, Belgium.
5
Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy.
6
Dipartimento di Oncologia e Emato-Oncologia, Università degli Studi di Milano, Milan, Italy.
7
Medical Oncology Department, Vall d'Hebron University Hospital and Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, Barcelona, Spain.
8
Medical Oncology, Institut de Cancérologie de l'Ouest (ICO) René Gauducheau, Nantes, France.
9
Department of Medical Oncology, Hôpital Saint Antoine; Sorbonne Universités, UMPC Paris 06 and GERCOR, Paris, France.

Abstract

Background:

Previous studies have reported the prognostic impact of primary tumor sidedness in metastatic colorectal cancer (mCRC) and its influence on cetuximab efficacy. The present retrospective analysis of two panitumumab trials investigated a possible association between tumor sidedness and treatment efficacy in first-line mCRC patients with RAS wild-type (WT) primary tumors.

Materials and methods:

Data from two randomized first-line panitumumab trials were analyzed for treatment outcomes by primary tumor sidedness for RAS WT patients. PRIME (phase 3; NCT00364013) compared panitumumab plus FOLFOX versus FOLFOX alone; PEAK (phase 2; NCT00819780) compared panitumumab plus FOLFOX versus bevacizumab plus FOLFOX. Primary tumors located in the cecum to transverse colon were coded as right-sided, while tumors located from the splenic flexure to rectum were considered left-sided.

Results:

Tumor sidedness ascertainment (RAS WT population) was 83% (n = 559/675); 78% of patients (n = 435) had left-sided and 22% (n = 124) had right-sided tumors. Patients with right-sided tumors did worse for all efficacy parameters compared with patients with left-sided disease in the RAS WT population and also in the RAS/BRAF WT subgroup. In patients with left-sided tumors, panitumumab provided better outcomes than the comparator treatment, including on median overall survival (PRIME: 30.3 versus 23.6 months, adjusted hazard ratio = 0.73, P = 0.0112; PEAK: 43.4 versus 32.0 months, adjusted hazard ratio = 0.77, P = 0.3125).

Conclusion:

The results of these retrospective analyses confirm that in RAS WT patients, right-sided primary tumors are associated with worse prognosis than left-sided tumors, regardless of first-line treatment received. RAS WT patients with left-sided tumors derive greater benefit from panitumumab-containing treatment than chemotherapy alone or combined with bevacizumab, including an overall survival advantage (treatment difference: PRIME 6.7 months; PEAK 11.4 months). No final conclusions regarding optimal treatment could be drawn for RAS WT patients with right-sided mCRC due to the relatively low number of paxtients. Further research in this field is warranted.

Trial registration (Clinicaltrials.gov):

PRIME (NCT00364013), PEAK (NCT00819780).

KEYWORDS:

RAS wild-type; first-line; metastatic colorectal cancer; panitumumab; tumor sidedness

Comment in

PMID:
28449055
PMCID:
PMC5834073
DOI:
10.1093/annonc/mdx119
[Indexed for MEDLINE]
Free PMC Article

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