title: Assessment of EGFR Mutation Status in Matched Plasma and Tumor Tissue of NSCLC Patients from a Phase I Study of Rociletinib (CO-1686).
abstract: The evaluation of plasma testing for the EGFR resistance mutation T790M in NSCLC patients has not been broadly explored. We investigated the detection of EGFR activating and T790M mutations in matched tumor tissue and plasma, mostly from patients with acquired resistance to first-generation EGFR inhibitors.
  
  
  
  Samples were obtained from two studies, an observational study and a phase I trial of rociletinib, a mutant-selective inhibitor of EGFR that targets both activating mutations and T790M. Plasma testing was performed with the cobas EGFR plasma test and BEAMing.
  
  
  
  The positive percent agreement (PPA) between cobas plasma and tumor results was 73% (55/75) for activating mutations and 64% (21/33) for T790M. The PPA between BEAMing plasma and tumor results was 82% (49/60) for activating mutations and 73% (33/45) for T790M. Presence of extrathoracic (M1b) versus intrathoracic (M1a/M0) disease was found to be strongly associated with ability to identify EGFR mutations in plasma (P < 0.001). Rociletinib objective response rates (ORR) were 52% [95% confidence interval (CI), 31 - 74%] for cobas tumor T790M-positive and 44% (95% CI, 25 - 63%) for BEAMing plasma T790M-positive patients. A drop in plasma-mutant EGFR levels to ≤10 molecules/mL was seen by day 21 of treatment in 7 of 8 patients with documented partial response.
  
  
  
  These findings suggest the cobas and BEAMing plasma tests can be useful tools for noninvasive assessment and monitoring of the T790M resistance mutation in NSCLC, and could complement tumor testing by identifying T790M mutations missed because of tumor heterogeneity or biopsy inadequacy. Clin Cancer Res; 22(10); 2386-95. ©2016 AACR.
authors.affiliation: Clovis Oncology Inc., San Francisco, California.
authors.forename: Chris
authors.initials: C
authors.lastname: Karlovich
authors.affiliation: University of California Los Angeles, Los Angeles, California. JWGoldman@mednet.ucla.edu hwakelee@stanford.edu.
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Goldman
authors.affiliation: Samsung Medical Center Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Jong-Mu
authors.initials: JM
authors.lastname: Sun
authors.affiliation: Clovis Oncology Inc., San Francisco, California.
authors.forename: Elaina
authors.initials: E
authors.lastname: Mann
authors.affiliation: Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Lecia V
authors.initials: LV
authors.lastname: Sequist
authors.affiliation: Medical University of Gdansk, Gdansk, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Konopa
authors.affiliation: Roche Molecular Systems, Pleasanton, California.
authors.forename: Wei
authors.initials: W
authors.lastname: Wen
authors.affiliation: Sysmex Inostics GmbH, Hamburg, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Angenendt
authors.affiliation: Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: Leora
authors.initials: L
authors.lastname: Horn
authors.affiliation: Sarah Cannon Research Institute, Nashville; Tennessee.
authors.forename: David
authors.initials: D
authors.lastname: Spigel
authors.affiliation: Institut Gustave Roussy, Villejuif, France.
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Soria
authors.affiliation: University of Melbourne, Melbourne, Australia.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Solomon
authors.affiliation: University of Colorado, Denver, Colorado.
authors.forename: D Ross
authors.initials: DR
authors.lastname: Camidge
authors.affiliation: Karmanos Cancer Institute/Wayne State University, Detroit, Michigan.
authors.forename: Shirish
authors.initials: S
authors.lastname: Gadgeel
authors.affiliation: Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Cloud
authors.initials: C
authors.lastname: Paweletz
authors.affiliation: Roche Molecular Systems, Pleasanton, California.
authors.forename: Lin
authors.initials: L
authors.lastname: Wu
authors.affiliation: Roche Molecular Systems, Pleasanton, California.
authors.forename: Sean
authors.initials: S
authors.lastname: Chien
authors.affiliation: Roche Molecular Systems, Pleasanton, California.
authors.forename: Patrick
authors.initials: P
authors.lastname: O'Donnell
authors.affiliation: Clovis Oncology Inc., San Francisco, California.
authors.forename: Shannon
authors.initials: S
authors.lastname: Matheny
authors.affiliation: Clovis Oncology Inc., San Francisco, California.
authors.forename: Darrin
authors.initials: D
authors.lastname: Despain
authors.affiliation: Clovis Oncology Inc., San Francisco, California.
authors.forename: Lindsey
authors.initials: L
authors.lastname: Rolfe
authors.affiliation: Clovis Oncology Inc., San Francisco, California.
authors.forename: Mitch
authors.initials: M
authors.lastname: Raponi
authors.affiliation: Clovis Oncology Inc., San Francisco, California.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Allen
authors.affiliation: Samsung Medical Center Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Keunchil
authors.initials: K
authors.lastname: Park
authors.affiliation: Stanford University, Stanford, California. JWGoldman@mednet.ucla.edu hwakelee@stanford.edu.
authors.forename: Heather
authors.initials: H
authors.lastname: Wakelee
mesh_terms: D000178:Acrylamides / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000187:drug effects / Q000235:genetics*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011743:Pyrimidines / Q000627:therapeutic use
chemical_list: D000178:Acrylamides; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; C000589977:rociletinib; C512478:EGFR protein, human; D066246:ErbB Receptors