title: Osimertinib benefit in EGFR-mutant NSCLC patients with T790M-mutation detected by circulating tumour DNA.
abstract: Approximately 50% of epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) patients treated with EGFR tyrosine kinase inhibitors (TKIs) will acquire resistance by the T790M mutation. Osimertinib is the standard of care in this situation. The present study assesses the efficacy of osimertinib when T790M status is determined in circulating cell-free tumour DNA (ctDNA) from blood samples in progressing advanced EGFR-mutant NSCLC patients.
  
  
  
  ctDNA T790M mutational status was assessed by Inivata InVision™ (eTAm-Seq™) assay in 48 EGFR-mutant advanced NSCLC patients with acquired resistance to EGFR TKIs without a tissue biopsy between April 2015 and April 2016. Progressing T790M-positive NSCLC patients received osimertinib (80 mg daily). The objectives were to assess the response rate to osimertinib according to Response Evaluation Criteria in Solid Tumours (RECIST) 1.1, the progression-free survival (PFS) on osimertinib, and the percentage of T790M positive in ctDNA.
  
  
  
  The ctDNA T790M mutation was detected in 50% of NSCLC patients. Among assessable patients, osimertinib gave a partial response rate of 62.5% and a stable disease rate of 37.5%. All responses were confirmed responses. After median follow up of 8 months, median PFS by RECIST criteria was not achieved (95% CI: 4-NA), with 6- and 12-months PFS of 66.7% and 52%, respectively.
  
  
  
  ctDNA from liquid biopsy can be used as a surrogate marker for T790M in tumour tissue.
authors.affiliation: Department of Medical Oncology, Gustave Roussy Cancer Campus, Villejuif, France.
authors.forename: J
authors.initials: J
authors.lastname: Remon
authors.affiliation: Radiology, Gustave Roussy, Université Paris-Saclay, Villejuif, France.
authors.forename: C
authors.initials: C
authors.lastname: Caramella
authors.affiliation: Translational Research Laboratory, AMMICA, INSERM US23/CNRS UNS3655, Gustave Roussy, Villejuif, France.
authors.forename: C
authors.initials: C
authors.lastname: Jovelet
authors.affiliation: Translational Research Laboratory, AMMICA, INSERM US23/CNRS UNS3655, Gustave Roussy, Villejuif, France.
authors.forename: L
authors.initials: L
authors.lastname: Lacroix
authors.affiliation: Inivata Ltd, Cambridge, UK.
authors.forename: A
authors.initials: A
authors.lastname: Lawson
authors.affiliation: Inivata Ltd, Cambridge, UK.
authors.forename: S
authors.initials: S
authors.lastname: Smalley
authors.affiliation: Inivata Ltd, Cambridge, UK.
authors.forename: K
authors.initials: K
authors.lastname: Howarth
authors.affiliation: Inivata Ltd, Cambridge, UK.|Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.
authors.forename: D
authors.initials: D
authors.lastname: Gale
authors.affiliation: Inivata Ltd, Cambridge, UK.
authors.forename: E
authors.initials: E
authors.lastname: Green
authors.affiliation: Inivata Ltd, Cambridge, UK.
authors.forename: V
authors.initials: V
authors.lastname: Plagnol
authors.affiliation: Inivata Ltd, Cambridge, UK.|Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.|Cambridge Cancer Centre, Cambridge, UK.
authors.forename: N
authors.initials: N
authors.lastname: Rosenfeld
authors.affiliation: Department of Medical Oncology, Gustave Roussy Cancer Campus, Villejuif, France.
authors.forename: D
authors.initials: D
authors.lastname: Planchard
authors.affiliation: Department of Medical Oncology, Gustave Roussy Cancer Campus, Villejuif, France.
authors.forename: M V
authors.initials: MV
authors.lastname: Bluthgen
authors.affiliation: Department of Medical Oncology, Gustave Roussy Cancer Campus, Villejuif, France.
authors.forename: A
authors.initials: A
authors.lastname: Gazzah
authors.affiliation: Department of Medical Oncology, Gustave Roussy Cancer Campus, Villejuif, France.
authors.forename: C
authors.initials: C
authors.lastname: Pannet
authors.affiliation: Department of Medical Oncology, Gustave Roussy Cancer Campus, Villejuif, France.
authors.forename: C
authors.initials: C
authors.lastname: Nicotra
authors.affiliation: Department of Medical Oncology, Gustave Roussy Cancer Campus, Villejuif, France.
authors.forename: E
authors.initials: E
authors.lastname: Auclin
authors.affiliation: Department of Medical Oncology, Gustave Roussy Cancer Campus, Villejuif, France.|University Paris-Sud and Gustave Roussy Cancer Campus, Villejuif, France.
authors.forename: J C
authors.initials: JC
authors.lastname: Soria
authors.affiliation: Department of Medical Oncology, Gustave Roussy Cancer Campus, Villejuif, France.|University Paris-Sud and Gustave Roussy Cancer Campus, Villejuif, France.
authors.forename: B
authors.initials: B
authors.lastname: Besse
mesh_terms: D000178:Acrylamides; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000814:Aniline Compounds; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D004252:DNA Mutational Analysis / Q000379:methods*; D004273:DNA, Neoplasm / Q000097:blood* / Q000235:genetics; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010879:Piperazines / Q000627:therapeutic use*; D007211:Indoles; D011743:Pyrimidines
chemical_list: D000178:Acrylamides; D000814:Aniline Compounds; D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D066246:ErbB Receptors; D010879:Piperazines; C000596361:osimertinib; D007211:Indoles; D011743:Pyrimidines; C512478:EGFR protein, human
keywords: EGFR mutation; T790M; ctDNA liquid biopsies; lung cancer; osimertinib