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Lung adenocarcinoma with ERBB2 exon 20 insertions: Comutations and immunogenomic features related to

Panwen Tian1, Hao Zeng1, Liyan Ji2

  • 1Department of Respiratory and Critical Care Medicine, Lung Cancer Treatment Center, West China Hospital, Sichuan University, Chengdu, China.

Lung Cancer (Amsterdam, Netherlands)
|August 17, 2021
PubMed
Abstract

Insights

Chemoimmunotherapy shows promise for ERBB2 exon 20 insertion lung cancer, despite low tumor mutational burden. Biomarkers like TMB and comutations can predict patient response to treatment.

Area of Science:

  • Oncology
  • Genomics
  • Immunotherapy

Background:

  • The genomic and immune characteristics of ERBB2 exon 20 insertion (ERBB2-ex20ins)-driven non-small cell lung cancer remain largely unknown.
  • Understanding these features is crucial for identifying effective treatment strategies, particularly for chemoimmunotherapy response.

Purpose of the Study:

  • To characterize the genomic landscape of ERBB2-ex20ins lung adenocarcinoma (LUAD).
  • To evaluate the clinical outcomes of chemoimmunotherapy in patients with ERBB2-ex20ins LUAD.
  • To identify potential biomarkers associated with response to chemoimmunotherapy.

Main Methods:

  • Next-generation sequencing (NGS) of 1021 cancer genes was used to analyze the genomic landscape.
  • Clinical outcomes of chemoimmunotherapy were assessed in 13 patients with stage IV ERBB2-ex20ins LUAD.
  • T cell receptor sequencing was employed to explore response biomarkers.

Main Results:

  • ERBB2-ex20ins mutations were found in 2.5% of LUAD patients, often with co-mutations (e.g., TP53).
  • These patients typically had low tumor mutational burden (TMB) and were PD-L1 negative.
  • Chemoimmunotherapy yielded an objective response rate of 31% and median progression-free survival of 8.0 months, with higher TMB correlating with better response.

Conclusions:

  • Chemoimmunotherapy demonstrates encouraging efficacy in ERBB2-ex20ins LUAD patients, even with low TMB and PD-L1 negativity.
  • A combination of TMB and co-mutations may serve as a predictive biomarker for chemoimmunotherapy benefit.
Keywords:
ChemoimmunotherapyERBB2 exon 20 insertionEfficacyLung adenocarcinomaPrognosisResponse

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