Clinical Impact of Hybrid Capture–Based Next-Generation Sequencing on Changes in Treatment Decisions in Lung Cancer

Autor: S. Geva, Maya Ilouze, Elizabeth Dudnik, Lior Soussan-Gutman, Anna Belilovski Rozenblum, Nir Peled, Addie Dvir
Rok vydání: 2017
Předmět:
Adult
Male
0301 basic medicine
Pulmonary and Respiratory Medicine
Oncology
medicine.medical_specialty
Lung Neoplasms
medicine.medical_treatment
Adenocarcinoma
Bioinformatics
Proto-Oncogene Mas
Targeted therapy
Young Adult
03 medical and health sciences
0302 clinical medicine
Internal medicine
Antineoplastic Combined Chemotherapy Protocols
Biomarkers
Tumor
medicine
Humans
Anaplastic lymphoma kinase
Molecular Targeted Therapy
Young adult
Lung cancer
Aged
Neoplasm Staging
Retrospective Studies
Aged
80 and over
Gene Rearrangement
business.industry
High-Throughput Nucleotide Sequencing
Retrospective cohort study
Sequence Analysis
DNA
Gene rearrangement
Immunotherapy
Middle Aged
Decision Support Systems
Clinical
Prognosis
medicine.disease
030104 developmental biology
030220 oncology & carcinogenesis
Mutation
Female
business
Follow-Up Studies
Zdroj: Journal of Thoracic Oncology. 12:258-268
ISSN: 1556-0864
Popis: Introduction 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. Methods 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. Results 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. Conclusions 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.
Databáze: OpenAIRE
Externí odkaz: