title: Comprehensive Genomic Profiling Identifies Frequent Drug-Sensitive EGFR Exon 19 Deletions in NSCLC not Identified by Prior Molecular Testing.
abstract: Reliable detection of drug-sensitive activating EGFR mutations is critical in the care of advanced non-small cell lung cancer (NSCLC), but such testing is commonly performed using a wide variety of platforms, many of which lack rigorous analytic validation.
  
  
  
  A large pool of NSCLC cases was assayed with well-validated, hybrid capture-based comprehensive genomic profiling (CGP) at the request of the individual treating physicians in the course of clinical care for the purpose of making therapy decisions. From these, 400 cases harboring EGFR exon 19 deletions (Δex19) were identified, and available clinical history was reviewed.
  
  
  
  Pathology reports were available for 250 consecutive cases with classical EGFR Δex19 (amino acids 743-754) and were reviewed to assess previous non-hybrid capture-based EGFR testing. Twelve of 71 (17%) cases with EGFR testing results available were negative by previous testing, including 8 of 46 (17%) cases for which the same biopsy was analyzed. Independently, five of six (83%) cases harboring C-helical EGFR Δex19 were previously negative. In a subset of these patients with available clinical outcome information, robust benefit from treatment with EGFR inhibitors was observed.
  
  
  
  CGP identifies drug-sensitive EGFR Δex19 in NSCLC cases that have undergone prior EGFR testing and returned negative results. Given the proven benefit in progression-free survival conferred by EGFR tyrosine kinase inhibitors in patients with these alterations, CGP should be considered in the initial presentation of advanced NSCLC and when previous testing for EGFR mutations or other driver alterations is negative. Clin Cancer Res; 22(13); 3281-5. ©2016 AACR.
authors.affiliation: Foundation Medicine Inc., Cambridge, Massachusetts.
authors.forename: Alexa B
authors.initials: AB
authors.lastname: Schrock
authors.affiliation: Foundation Medicine Inc., Cambridge, Massachusetts.
authors.forename: Garrett M
authors.initials: GM
authors.lastname: Frampton
authors.affiliation: Cone Health, Cancer Center at Wesley Long, Greensboro, North Carolina.
authors.forename: Dana
authors.initials: D
authors.lastname: Herndon
authors.affiliation: Foundation Medicine Inc., Cambridge, Massachusetts.
authors.forename: Joel R
authors.initials: JR
authors.lastname: Greenbowe
authors.affiliation: Foundation Medicine Inc., Cambridge, Massachusetts.
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.affiliation: Foundation Medicine Inc., Cambridge, Massachusetts.
authors.forename: Doron
authors.initials: D
authors.lastname: Lipson
authors.affiliation: Foundation Medicine Inc., Cambridge, Massachusetts.
authors.forename: Roman
authors.initials: R
authors.lastname: Yelensky
authors.affiliation: Foundation Medicine Inc., Cambridge, Massachusetts.
authors.forename: Zachary R
authors.initials: ZR
authors.lastname: Chalmers
authors.affiliation: Foundation Medicine Inc., Cambridge, Massachusetts.
authors.forename: Juliann
authors.initials: J
authors.lastname: Chmielecki
authors.affiliation: Foundation Medicine Inc., Cambridge, Massachusetts.
authors.forename: Julia A
authors.initials: JA
authors.lastname: Elvin
authors.affiliation: Department of Oncology, Rambam Health Care Campus, Haifa, Israel.
authors.forename: Mira
authors.initials: M
authors.lastname: Wollner
authors.affiliation: Teva Pharmaceuticals, Petah Tikva, Israel.
authors.forename: Addie
authors.initials: A
authors.lastname: Dvir
authors.affiliation: Teva Pharmaceuticals, Petah Tikva, Israel.
authors.forename: Lior Soussan
authors.initials: LS
authors.lastname: -Gutman
authors.affiliation: Georgia Cancer Specialists, Marietta, Georgia.
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Bordoni
authors.affiliation: Thoracic Cancer Unit, Davidoff Cancer Center, Petach Tiqwa, Israel.
authors.forename: Nir
authors.initials: N
authors.lastname: Peled
authors.affiliation: Comprehensive Cancer Centers of Nevada, Las Vegas, Nevada.
authors.forename: Fadi
authors.initials: F
authors.lastname: Braiteh
authors.affiliation: Memorial Healthcare System, Pembroke Pines, Florida.
authors.forename: Luis
authors.initials: L
authors.lastname: Raez
authors.affiliation: Foundation Medicine Inc., Cambridge, Massachusetts.
authors.forename: Rachel
authors.initials: R
authors.lastname: Erlich
authors.affiliation: Chao Comprehensive Cancer Center, Irvine, California.
authors.forename: Sai-Hong Ignatius
authors.initials: SH
authors.lastname: Ou
authors.affiliation: Cone Health, Cancer Center at Wesley Long, Greensboro, North Carolina.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Mohamed
authors.affiliation: Foundation Medicine Inc., Cambridge, Massachusetts. Albany Medical College, Albany, New York.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Ross
authors.affiliation: Foundation Medicine Inc., Cambridge, Massachusetts.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Stephens
authors.affiliation: Foundation Medicine Inc., Cambridge, Massachusetts. Vmiller@foundationmedicine.com sali@foundationmedicine.com.
authors.forename: Siraj M
authors.initials: SM
authors.lastname: Ali
authors.affiliation: Foundation Medicine Inc., Cambridge, Massachusetts. Vmiller@foundationmedicine.com sali@foundationmedicine.com.
authors.forename: Vincent A
authors.initials: VA
authors.lastname: Miller
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001483:Base Sequence / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics*; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D017384:Sequence Deletion / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; C512478:EGFR protein, human; D066246:ErbB Receptors