title: Clinical Impact of Hybrid Capture-Based Next-Generation Sequencing on Changes in Treatment Decisions in Lung Cancer.
abstract: Targeted therapy significantly prolongs survival in lung adenocarcinoma. Current diagnostic guidelines include only EGFR and anaplastic lymphoma receptor tyrosine kinase gene (ALK) testing. Next-generation sequencing (NGS) reveals more actionable genomic alterations than do standard diagnostic methods. Data on the influence of hybrid capture (HC)-based NGS on treatment are limited, and we investigated its impact on treatment decisions and clinical outcomes.
  
  
  
  This retrospective study included patients with advanced lung cancer on whom HC-based NGS was performed between November 2011 and October 2015. Demographic and clinicopathologic characteristics, treatments, and outcome data were collected.
  
  
  
  A total of 101 patients were included (median age 63 years [53% females, 45% never-smokers, and 85% with adenocarcinoma]). HC-based NGS was performed upfront and after EGFR/ALK testing yielded negative or inconclusive results in 15% and 85% of patients, respectively. In 51.5% of patients, HC-based NGS was performed before first-line therapy, and in 48.5%, it was performed after treatment failure. HC-based NGS identified clinically actionable genomic alterations in 50% of patients, most frequently in EGFR (18%), Ret proto-oncogene (RET) (9%), ALK (8%), Mesenchymal-epithelial transition factor (MET) receptor tyrosine kinase gene (6%), and erb-b2 receptor tyrosine kinase 2 gene (ERBB2) (5%). In 15 patients, it identified EGFR/ALK aberrations after negative results of prior standard testing. Treatment strategy was changed for 43 patients (42.6%). The overall response rate in these patients was 65% (complete response 14.7%, partial response 50%). Median survival was not reached. Immunotherapy was administered in 33 patients, mostly without an actionable driver, with a presenting disease control rate of 32%, and with an association with tumor mutation burden.
  
  
  
  HC-based NGS influenced treatment decisions in close to half of the patients with lung adenocarcinoma and was associated with an overall response rate of 65%, which may translate into a survival benefit.
authors.affiliation: Thoracic Cancer Service, Davidoff Cancer Center, Rabin Medical Center, Petah Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Anna Belilovski
authors.initials: AB
authors.lastname: Rozenblum
authors.affiliation: Thoracic Cancer Service, Davidoff Cancer Center, Rabin Medical Center, Petah Tikva, Israel.
authors.forename: Maya
authors.initials: M
authors.lastname: Ilouze
authors.affiliation: Thoracic Cancer Service, Davidoff Cancer Center, Rabin Medical Center, Petah Tikva, Israel.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Dudnik
authors.affiliation: Teva Pharmaceutical Industries Ltd., Shoam, Israel.
authors.forename: Addie
authors.initials: A
authors.lastname: Dvir
authors.affiliation: Teva Pharmaceutical Industries Ltd., Shoam, Israel.
authors.forename: Lior
authors.initials: L
authors.lastname: Soussan-Gutman
authors.affiliation: Thoracic Cancer Service, Davidoff Cancer Center, Rabin Medical Center, Petah Tikva, Israel.
authors.forename: Smadar
authors.initials: S
authors.lastname: Geva
authors.affiliation: Thoracic Cancer Service, Davidoff Cancer Center, Rabin Medical Center, Petah Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Electronic address: nirp@post.tau.ac.il.
authors.forename: Nir
authors.initials: N
authors.lastname: Peled
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics*; D020000:Decision Support Systems, Clinical; D005260:Female; D005500:Follow-Up Studies; D015321:Gene Rearrangement; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009154:Mutation; D009367:Neoplasm Staging; D011379:Prognosis; D000090063:Proto-Oncogene Mas; D012189:Retrospective Studies; D017422:Sequence Analysis, DNA / Q000379:methods; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas
keywords: Driver mutations; Immunotherapy; Next-generation sequencing; Oncogenic drivers; Precision/personalized medicine; Targeted therapy