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Advanced Lung Adenocarcinoma Patient with ERBB2 Amplification Identified by Comprehensive Genomic Profiling Benefits from Trastuzumab.

ABSTRACT: For non-small-cell lung cancer (NSCLC) patients without established actionable alterations in genes such as EGFR or ALK, options for targeted therapy remain limited in clinical practice. About 5% of lung adenocarcinoma patients have tumors with ERBB2 genetic alterations, with even fewer patients harboring ERBB2 amplification. Currently, clinical trials mainly use IHC, FISH, or mutation testing to identify potential responders to ERBB2-targeting agents. The use of next-generation sequencing (NGS) to detect ERBB2 alterations, including copy number variants, is rare. In this study, we present an EGFR- and ALK-negative advanced NSCLC case for which we conducted comprehensive tumor genomic profiling to identify potentially actionable alterations. The tumor harbored an ERBB2 amplification, and trastuzumab-based therapy resulted in an excellent response, with a necrotic regression of the patient's lung lesion. Although he developed brain metastasis four months after trastuzumab initiation, he survived for an additional period of eight months without local recurrence or other systemic metastasis. This case report shows that the use of comprehensive genetic testing enables the identification of rare actionable alterations in NSCLC patients without other options for targeted treatment.

SUBMITTER: Tao CW

PROVIDER: S-EPMC7071810 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Advanced Lung Adenocarcinoma Patient with ERBB2 Amplification Identified by Comprehensive Genomic Profiling Benefits from Trastuzumab.

Tao Chi-Wei CW Chen Mei-Yin MY Tseng Ching-Min CM Lapke Nina N Chen Shu-Jen SJ Tan Kien Thiam KT

Case reports in oncological medicine 20200301

For non-small-cell lung cancer (NSCLC) patients without established actionable alterations in genes such as EGFR or ALK, options for targeted therapy remain limited in clinical practice. About 5% of lung adenocarcinoma patients have tumors with ERBB2 genetic alterations, with even fewer patients harboring ERBB2 amplification. Currently, clinical trials mainly use IHC, FISH, or mutation testing to identify potential responders to ERBB2-targeting agents. The use of next ...[more]

PMID: 32190395

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Project description:Amplification (amp) of MET can be observed in cases of focal gene copy number gain, such as MET-driven amp, or with a gain of chromosome 7, such as aneuploidy. Several studies have shown that only high-level focal MET amp (MET/CEP7 ratio ≥5) is oncogenic, with such tumors responding to targeted therapy. However, there are few reports on how to distinguish between focal amplification and aneuploidy using next-generation sequencing (NGS). A total of 1025 patients with advanced solid tumors (typically pre-treated) were tested with a non-invasive comprehensive cfDNA NGS panel (Guardant360) from July 2014 to June 2019. Since bioinformatics upgrades of Guardant360 were undergoing in September 2018, focal MET amp was determined by our independent algorithm using the cohorts tested before September 2018 (291 patients), and validation was performed in the remaining cohort (734 patients). MET alterations (alts) associated with aberrant signaling were found in 110 patients (10.7%) among nine different cancer types, most commonly in non-small cell (12.2%, 62/510) and small cell (33.3%, 3/9) lung cancers, gastroesophageal cancer (19.4%, 7/36), and prostate adenocarcinoma (15.6%; 5/32). Among 291 patients tested before September 2018, 37 (12.7%) had MET alts. Among these, 24 (64.9%) had amps, 5 (13.5%) had exon 14 skipping, and 13 (35.1%) had single nucleotide variants (SNVs). Co-alterations, such as amp + SNVs, were found in four samples (10.8%). Among 24 MET amps, 29.2% (7/24) were focal according to our algorithm. MET copy number was significantly higher with focal amp compared to non-focal amp (mean copy number 3.26 vs. 2.44, respectively, p = 0.00304). In 734 patients tested after September 2018, our definition of focal MET amp was detected in 4.2% (31/734). Overall, focal amplification based on our algorithm was 3.7% (=38/1025). This study describes an approach to distinguish focal and non-focal MET amplification using comprehensive genomic profiling of cfDNA in advanced cancer patients. Focal MET amp accounted for ~30% of all MET amp, which was found in 3.7% of patients with diverse cancers and was associated with a higher plasma copy number. Clinical studies are warranted to assess the clinical utility of targeted therapies for tumors with focal MET amplification detected by NGS of cfDNA.

Dataset Information

Advanced Lung Adenocarcinoma Patient with ERBB2 Amplification Identified by Comprehensive Genomic Profiling Benefits from Trastuzumab.

Publications

Advanced Lung Adenocarcinoma Patient with <i>ERBB2</i> Amplification Identified by Comprehensive Genomic Profiling Benefits from Trastuzumab.

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