Prospective Clinical Integration of an Amplicon-Based Next-Generation Sequencing Method to Select Advanced Non–Small-Cell Lung Cancer Patients for Genotype-Tailored Treatments

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Abstract

Introduction

A substantial fraction of non–small-cell lung cancers (NSCLCs) harbor targetable genetic alterations. In this study, we analyzed the feasibility and clinical utility of integrating a next-generation sequencing (NGS) panel into our routine lung cancer molecular subtyping algorithm.

Patients and Methods

After routine pathologic and molecular subtyping, we implemented an amplicon-based gene panel for DNA analysis covering mutational hot spots in 22 cancer genes in consecutive advanced-stage NSCLCs.

Results

We analyzed 109 tumors using NGS between December 2014 and January 2016. Fifty-six patients (51%) were treatment-naive and 82 (75%) had lung adenocarcinomas. In 89 cases (82%), we used samples derived from lung cancer diagnostic procedures. We obtained successful sequencing results in 95 cases (87%). As part of our routine lung cancer molecular subtyping protocol, single-gene testing for EGFR, ALK, and ROS1 was attempted in nonsquamous and 3 squamous-cell cancers (n = 92). Sixty-nine of 92 samples (75%) had sufficient tissue to complete ALK and ROS1 immunohistochemistry (IHC) and NGS. With the integration of the gene panel, 40 NSCLCs (37%) in the entire cohort and 30 NSCLCs (40%) fully tested for ALK and ROS1 IHC and NGS had actionable mutations. KRAS (24%) and EGFR (10%) were the most frequently mutated actionable genes. Ten patients (9%) received matched targeted therapies, 6 (5%) in clinical trials.

Conclusion

The combination of IHC tests for ALK and ROS1 and amplicon-based NGS is applicable in routine clinical practice, enabling patient selection for genotype-tailored treatments.

Micro-Abstract

A broad clinical applicability of some next-generation sequencing (NGS) assays might be limited by analytic difficulties and tissue amount requirements. We successfully applied an amplicon-based NGS panel in advanced non–small-cell lung cancers (NSCLCs; n = 109). In nonsquamous tumors, immunohistochemistry tests for ALK and ROS1 with DNA NGS were combined. Forty NSCLCs had actionable mutations and 10 patients received tailored treatments.

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