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Durable response to afatinib in advanced lung adenocarcinoma harboring a novel NPTN-NRG1 fusion: a case report
Xin Nie1, Ping Zhang1, Zhixin Bie2
1Department of Medical Oncology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, No. 1 DaHua Road, Beijing, 100730, China.
Background:
NRG1 fusions are rare oncogenic drivers in solid tumors, and the incidence of NRG1 fusions in non-small cell lung cancer (NSCLC) was 0.26%. It is essential to explore potential therapeutic strategies and efficacy predictors for NRG1 fusion-positive cancers.
Case Presentation:
We report an advanced lung adenocarcinoma patient harboring a novel NPTN-NRG1 fusion identified by RNA-based next-generation sequencing (NGS), which was not detected by DNA-based NGS at initial diagnosis. Transcriptomics data of the tissue biopsy showed NRG1α isoform accounted for 30% of total NRG1 reads, and NRG1β isoform was undetectable. The patient received afatinib as fourth-line treatment and received a progression-free survival (PFS) of 14 months.
Conclusions:
This report supports afatinib can provide potential benefit for NRG1 fusion patients, and RNA-based NGS is an accurate and cost-effective strategy for fusion detection and isoform identification.
Insights
A novel NPTN-NRG1 fusion was identified in lung cancer using RNA-based next-generation sequencing (NGS). Afatinib treatment resulted in a 14-month progression-free survival, suggesting its potential benefit for NRG1 fusion-positive cancers.
Area of Science:
- Oncology
- Genomics
- Molecular Diagnostics
Background:
- NRG1 fusions are rare oncogenic drivers in solid tumors, occurring in 0.26% of non-small cell lung cancer (NSCLC) cases.
- Identifying therapeutic strategies and efficacy predictors for NRG1 fusion-positive cancers is crucial.
Observation:
- A patient with advanced lung adenocarcinoma presented with a novel NPTN-NRG1 fusion.
- This fusion was detected by RNA-based next-generation sequencing (NGS) but missed by DNA-based NGS.
- Transcriptomics revealed NRG1α isoform dominance (30% of total NRG1 reads), with undetectable NRG1β.
Findings:
- The patient received afatinib as fourth-line treatment.
- Afatinib treatment led to a progression-free survival (PFS) of 14 months.
Implications:
- Afatinib may offer potential therapeutic benefits for patients with NRG1 fusions.
- RNA-based NGS is a valuable and cost-effective tool for detecting fusions and identifying specific isoforms.
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