Lung adenocarcinoma with ERBB2 exon 20 insertions: Comutations and immunogenomic features related to chemoimmunotherapy.
Lung Cancer
; 160: 50-58, 2021 10.
Article
em En
| MEDLINE
| ID: mdl-34403912
ABSTRACT
BACKGROUND:
The genomic mutation and immune feature landscape of ERBB2 exon 20 insertion (ERBB2-ex20ins)-driven non-small cell lung cancer and the features associated with the response to chemoimmunotherapy are currently unknown.METHODS:
The genomic landscape of ERBB2-ex20ins lung adenocarcinoma (LUAD) patients was characterized by next-generation sequencing (NGS) of 1021 cancer genes. The clinical outcomes of chemoimmunotherapy were evaluated among 13 patients with stage IV ERBB2-ex20ins LUAD, and potential biomarkers of the response to chemoimmunotherapy were explored using NGS and T cell receptor sequencing.RESULTS:
Among 8247 LUAD patients, 207 (2.5%) had ERBB2-ex20ins, of whom 181 (87.4%) harbored more than one comutation. The most common comutations were in TP53. Patients with ERBB2-ex20ins had a low tumor mutational burden (TMB; median, 4.2 mutations/Mb), and most (66.7%) were PD-L1 negative. Thirteen of the 207 patients received chemoimmunotherapy, for whom the objective response rate, disease control rate, and median progression-free survival were 31%, 77%, and 8.0â¯months, respectively. Responders exhibited a higher TMB and a trend toward lower clonality in tumors compared with nonresponders (pâ¯=â¯0.0067 and pâ¯=â¯0.085, respectively). A high TMB combined with mutations in DNA damage repair pathways and SWI/SNF chromatin remodeling complexes was associated with a benefit from chemoimmunotherapy.CONCLUSIONS:
The efficacy and outcome of chemoimmunotherapy were encouraging among ERBB2-ex20ins LUAD patients, who were characterized by low TMB and negative PD-L1 expression. The combination of TMB and comutations is a potential biomarker to identify patients who will benefit from chemoimmunotherapy.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Carcinoma Pulmonar de Células não Pequenas
/
Adenocarcinoma de Pulmão
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Neoplasias Pulmonares
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article