title: Extended RAS Gene Mutation Testing in Metastatic Colorectal Carcinoma to Predict Response to Anti-Epidermal Growth Factor Receptor Monoclonal Antibody Therapy: American Society of Clinical Oncology Provisional Clinical Opinion Update 2015.
abstract: OBJECTIVE
  An American Society of Clinical Oncology Provisional Clinical Opinion (PCO) offers timely clinical direction after publication or presentation of potentially practice-changing data from major studies. This PCO update addresses the utility of extended RAS gene mutation testing in patients with metastatic colorectal cancer (mCRC) to detect resistance to anti-epidermal growth factor receptor (EGFR) monoclonal antibody (MoAb) therapy.
  
  
  METHODS
  Recent results from phase II and III clinical trials in mCRC demonstrate that patients whose tumors harbor RAS mutations in exons 2 (codons 12 and 13), 3 (codons 59 and 61), and 4 (codons 117 and 146) are unlikely to benefit from therapy with MoAbs directed against EGFR, when used as monotherapy or combined with chemotherapy.
  
  
  METHODS
  In addition to the evidence reviewed in the original PCO, 11 systematic reviews with meta-analyses, two retrospective analyses, and two health technology assessments based on a systematic review were obtained. These evaluated the outcomes for patients with mCRC with no mutation detected or presence of mutation in additional exons in KRAS and NRAS. PCO: All patients with mCRC who are candidates for anti-EGFR antibody therapy should have their tumor tested in a Clinical Laboratory Improvement Amendments-certified laboratory for mutations in both KRAS and NRAS exons 2 (codons 12 and 13), 3 (codons 59 and 61), and 4 (codons 117 and 146). The weight of current evidence indicates that anti-EGFR MoAb therapy should only be considered for treatment of patients whose tumor is determined to not have mutations detected after such extended RAS testing.
authors.affiliation: Carmen J. Allegra, University of Florida, Gainesville, FL; R. Bryan Rumble, Pamela B. Mangu, and Richard L. Schilsky, American Society of Clinical Oncology; Nancy Roach, Fight Colorectal Cancer, Alexandria, VA; Stanley R. Hamilton, University of Texas MD Anderson Cancer Center, Houston, TX; and Alexander Hantel, Edward Cancer Center, Naperville, IL.
authors.forename: Carmen J
authors.initials: CJ
authors.lastname: Allegra
authors.affiliation: Carmen J. Allegra, University of Florida, Gainesville, FL; R. Bryan Rumble, Pamela B. Mangu, and Richard L. Schilsky, American Society of Clinical Oncology; Nancy Roach, Fight Colorectal Cancer, Alexandria, VA; Stanley R. Hamilton, University of Texas MD Anderson Cancer Center, Houston, TX; and Alexander Hantel, Edward Cancer Center, Naperville, IL.
authors.forename: R Bryan
authors.initials: RB
authors.lastname: Rumble
authors.affiliation: Carmen J. Allegra, University of Florida, Gainesville, FL; R. Bryan Rumble, Pamela B. Mangu, and Richard L. Schilsky, American Society of Clinical Oncology; Nancy Roach, Fight Colorectal Cancer, Alexandria, VA; Stanley R. Hamilton, University of Texas MD Anderson Cancer Center, Houston, TX; and Alexander Hantel, Edward Cancer Center, Naperville, IL.
authors.forename: Stanley R
authors.initials: SR
authors.lastname: Hamilton
authors.affiliation: Carmen J. Allegra, University of Florida, Gainesville, FL; R. Bryan Rumble, Pamela B. Mangu, and Richard L. Schilsky, American Society of Clinical Oncology; Nancy Roach, Fight Colorectal Cancer, Alexandria, VA; Stanley R. Hamilton, University of Texas MD Anderson Cancer Center, Houston, TX; and Alexander Hantel, Edward Cancer Center, Naperville, IL.
authors.forename: Pamela B
authors.initials: PB
authors.lastname: Mangu
authors.affiliation: Carmen J. Allegra, University of Florida, Gainesville, FL; R. Bryan Rumble, Pamela B. Mangu, and Richard L. Schilsky, American Society of Clinical Oncology; Nancy Roach, Fight Colorectal Cancer, Alexandria, VA; Stanley R. Hamilton, University of Texas MD Anderson Cancer Center, Houston, TX; and Alexander Hantel, Edward Cancer Center, Naperville, IL.
authors.forename: Nancy
authors.initials: N
authors.lastname: Roach
authors.affiliation: Carmen J. Allegra, University of Florida, Gainesville, FL; R. Bryan Rumble, Pamela B. Mangu, and Richard L. Schilsky, American Society of Clinical Oncology; Nancy Roach, Fight Colorectal Cancer, Alexandria, VA; Stanley R. Hamilton, University of Texas MD Anderson Cancer Center, Houston, TX; and Alexander Hantel, Edward Cancer Center, Naperville, IL.
authors.forename: Alexander
authors.initials: A
authors.lastname: Hantel
authors.affiliation: Carmen J. Allegra, University of Florida, Gainesville, FL; R. Bryan Rumble, Pamela B. Mangu, and Richard L. Schilsky, American Society of Clinical Oncology; Nancy Roach, Fight Colorectal Cancer, Alexandria, VA; Stanley R. Hamilton, University of Texas MD Anderson Cancer Center, Houston, TX; and Alexander Hantel, Edward Cancer Center, Naperville, IL.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Schilsky
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D005091:Exons; D020558:GTP Phosphohydrolases / Q000235:genetics; D011905:Genes, ras / Q000235:genetics*; D005820:Genetic Testing; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics; D015201:Meta-Analysis as Topic; D058990:Molecular Targeted Therapy / Q000379:methods; D009154:Mutation; D011237:Predictive Value of Tests; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D012189:Retrospective Studies
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; C117307:KRAS protein, human; D008565:Membrane Proteins; C512478:EGFR protein, human; D066246:ErbB Receptors; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)