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

Abstract

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.

Keywords: Driver mutations; Immunotherapy; Next-generation sequencing; Oncogenic drivers; Precision/personalized medicine; Targeted therapy.