Open AccessLocation of Primary Tumor and Benefit From Anti‐Epidermal Growth Factor Receptor Monoclonal Antibodies in Patients With RAS and BRAF Wild‐Type Metastatic Colorectal Cancer
Author(s) -
Moretto Roberto,
Cremolini Chiara,
Rossini Daniele,
Pietrantonio Filippo,
Battaglin Francesca,
Mennitto Alessia,
Bergamo Francesca,
Loupakis Fotios,
Marmorino Federica,
Berenato Rosa,
Marsico Valentina Angela,
Caporale Marta,
Antoniotti Carlotta,
Masi Gianluca,
Salvatore Lisa,
Borelli Beatrice,
Fontanini Gabriella,
Lonardi Sara,
De Braud Filippo,
Falcone Alfredo
Publication year - 2016
Publication title -
the oncologist
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.176
H-Index - 164
eISSN - 1549-490X
pISSN - 1083-7159
DOI - 10.1634/theoncologist.2016-0084
Subject(s) - medicine , cetuximab , irinotecan , colorectal cancer , panitumumab , oncology , epidermal growth factor receptor , hazard ratio , primary tumor , response evaluation criteria in solid tumors , cancer , metastasis , confidence interval , chemotherapy , progressive disease
. Right‐ and left‐sided colorectal cancers (CRCs) differ in clinical and molecular characteristics. Some retrospective analyses suggested that patients with right‐sided tumors derive less benefit from anti‐epidermal growth factor receptor (EGFR) antibodies; however, molecular selection in those studies was not extensive. Patients and Methods. Patients with RAS and BRAF wild‐type metastatic CRC (mCRC) who were treated with single‐agent anti‐EGFRs or with cetuximab‐irinotecan (if refractory to previous irinotecan) were included in the study. Differences in outcome between patients with right‐ and left‐sided tumors were investigated. Results. Of 75 patients, 14 and 61 had right‐ and left‐sided tumors, respectively. None of the right‐sided tumors responded according to RECIST, compared with 24 left‐sided tumors (overall response rate: 0% vs. 41%; p = .0032), and only 2 patients with right‐sided tumors (15%) versus 47 patients with left‐sided tumors (80%) achieved disease control ( p < .0001). The median duration of progression‐free survival was 2.3 and 6.6 months in patients with right‐sided and left‐sided tumors, respectively (hazard ratio: 3.97; 95% confidence interval: 2.09–7.53; p < .0001). Conclusion. Patients with right‐sided RAS and BRAF wild‐type mCRC seemed to derive no benefit from single‐agent anti‐EGFRs. Implications for Practice: Right‐ and left‐sided colorectal tumors have peculiar epidemiological and clinicopathological characteristics, distinct gene expression profiles and genetic alterations, and different prognoses. This study assessed the potential predictive impact of primary tumor site with regard to anti‐epidermal growth factor receptor (EGFR) monoclonal antibody treatment in patients with RAS and BRAF wild‐type metastatic colorectal cancer. The results demonstrated the lack of activity of anti‐EGFRs in RAS and BRAF wild‐type, right‐sided tumors, thus suggesting a potential role for primary tumor location in driving treatment choices.