title: Location of Primary Tumor and Benefit From Anti-Epidermal Growth Factor Receptor Monoclonal Antibodies in Patients With RAS and BRAF Wild-Type Metastatic Colorectal Cancer.
abstract: 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 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.
  
  
  
  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).
  
  
  
  Patients with right-sided RAS and BRAF wild-type mCRC seemed to derive no benefit from single-agent anti-EGFRs.
  
  
  
  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.
authors.affiliation: Polo Oncologico, Azienda Ospedaliero-Universitaria Pisana, Istituto Toscano Tumori, Pisa, Italy University of Pisa, Pisa, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Moretto
authors.affiliation: Polo Oncologico, Azienda Ospedaliero-Universitaria Pisana, Istituto Toscano Tumori, Pisa, Italy University of Pisa, Pisa, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Cremolini
authors.affiliation: Polo Oncologico, Azienda Ospedaliero-Universitaria Pisana, Istituto Toscano Tumori, Pisa, Italy University of Pisa, Pisa, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Rossini
authors.affiliation: Medical Oncology Department, Fondazione Istituti di Ricovero e Cura a Carattere Scientifico, Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Pietrantonio
authors.affiliation: Unit of Medical Oncology 1, Istituto Oncologico Veneto, Istituti di Ricovero e Cura a Carattere Scientifico, Padua, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Battaglin
authors.affiliation: Medical Oncology Department, Fondazione Istituti di Ricovero e Cura a Carattere Scientifico, Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Mennitto
authors.affiliation: Unit of Medical Oncology 1, Istituto Oncologico Veneto, Istituti di Ricovero e Cura a Carattere Scientifico, Padua, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Bergamo
authors.affiliation: Polo Oncologico, Azienda Ospedaliero-Universitaria Pisana, Istituto Toscano Tumori, Pisa, Italy University of Pisa, Pisa, Italy.
authors.forename: Fotios
authors.initials: F
authors.lastname: Loupakis
authors.affiliation: Polo Oncologico, Azienda Ospedaliero-Universitaria Pisana, Istituto Toscano Tumori, Pisa, Italy University of Pisa, Pisa, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Marmorino
authors.affiliation: Medical Oncology Department, Fondazione Istituti di Ricovero e Cura a Carattere Scientifico, Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Rosa
authors.initials: R
authors.lastname: Berenato
authors.affiliation: Unit of Medical Oncology 1, Istituto Oncologico Veneto, Istituti di Ricovero e Cura a Carattere Scientifico, Padua, Italy.
authors.forename: Valentina Angela
authors.initials: VA
authors.lastname: Marsico
authors.affiliation: Medical Oncology Department, Fondazione Istituti di Ricovero e Cura a Carattere Scientifico, Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Caporale
authors.affiliation: Polo Oncologico, Azienda Ospedaliero-Universitaria Pisana, Istituto Toscano Tumori, Pisa, Italy University of Pisa, Pisa, Italy.
authors.forename: Carlotta
authors.initials: C
authors.lastname: Antoniotti
authors.affiliation: Polo Oncologico, Azienda Ospedaliero-Universitaria Pisana, Istituto Toscano Tumori, Pisa, Italy University of Pisa, Pisa, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Masi
authors.affiliation: Polo Oncologico, Azienda Ospedaliero-Universitaria Pisana, Istituto Toscano Tumori, Pisa, Italy University of Pisa, Pisa, Italy.
authors.forename: Lisa
authors.initials: L
authors.lastname: Salvatore
authors.affiliation: Polo Oncologico, Azienda Ospedaliero-Universitaria Pisana, Istituto Toscano Tumori, Pisa, Italy University of Pisa, Pisa, Italy.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Borelli
authors.affiliation: Division of Pathology, Department of Surgical, Medical, Molecular Pathology, and Critical Area, University of Pisa, Pisa, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Fontanini
authors.affiliation: Unit of Medical Oncology 1, Istituto Oncologico Veneto, Istituti di Ricovero e Cura a Carattere Scientifico, Padua, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Lonardi
authors.affiliation: Medical Oncology Department, Fondazione Istituti di Ricovero e Cura a Carattere Scientifico, Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: De Braud
authors.affiliation: Polo Oncologico, Azienda Ospedaliero-Universitaria Pisana, Istituto Toscano Tumori, Pisa, Italy University of Pisa, Pisa, Italy alfredo.falcone@med.unipi.it.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Falcone
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D000068818:Cetuximab / Q000008:administration & dosage / Q000009:adverse effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics*; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D009382:Neoplasms, Unknown Primary / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C117307:KRAS protein, human; D008565:Membrane Proteins; D000077146:Irinotecan; C512478:EGFR protein, human; D066246:ErbB Receptors; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras); D000068818:Cetuximab; D002166:Camptothecin
keywords: Anti-EGFR monoclonal antibodies; Left-sided tumor; Metastatic colorectal cancer; Right-sided tumor