&lt;p&gt;Response to Afatinib in a Patient with Non-Small Cell Lung Cancer Harboring HER2 R896G Mutation: A Case Report&lt;/p&gt;

Li, Gang; Ge, Hongfei; Yan, Zhengqing; Wang, Guoqiang; Wu, Xiaomai; Lv, Dongqing

doi:10.2147/ott.s228726

Cited by 6 publications

(5 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…And L655V is close to V659/G660, which were demonstrated to be sensitive to afatinib (16). One lung squamous cell carcinoma patient with a HER2 R896G (exon 22) mutation had a long PFS of 14.5 months, which was recently reported as a case report (20). Another patient with a M960V (exon 24) mutation received afatinib as third-line therapy, and achieved a PR and a PFS of 7.1 months.…”

Section: Discussionmentioning

confidence: 87%

Efficacy and Resistance of Afatinib in Chinese Non-Small Cell Lung Cancer Patients With HER2 Alterations: A Multicenter Retrospective Study

Song

Chen³

et al. 2021

Front. Oncol.

Self Cite

View full text Add to dashboard Cite

BackgroundNon-small cell lung cancer (NSCLC) patients with HER2 mutations and amplification may benefit from HER2-targeted therapy, including afatinib. However, the data regarding the clinical activity of afatinib in Chinese patients with NSCLC harboring HER2 alterations are limited.Patients and methodsWe retrospectively included metastatic NSCLC patients harboring HER2 alterations who treated with afatinib. The clinical outcomes included overall response rate (ORR), progression-free survival (PFS) and overall survival (OS). The genomic profiling data after progression on afatinib were analyzed.ResultsWe included 54 patients harboring HER2 mutations and 12 patients harboring HER2 amplification. The ORR was 24% (95% CI, 16–36%), the median PFS was 3.3 months (95% CI, 2.2–4.4), and the median OS was 13.9 months (95% CI, 11.4–16.5). Patients with HER2 exon 20 mutations had numerically worse ORR (17% vs 42%), shorter PFS (2.6 vs 5.8 months, HR, 2.5; 95% CI, 1.2–5.5; P = 0.015) and OS (12.9 vs 33.3 months, HR, 4.4; 95% CI, 1.3–14.8; P = 0.009) than patients with other mutations. For HER2-amplified patients, the ORR was 33% (95% CI, 14–61%), the median PFS was 3.3 months (95% CI, 2.6–4.0), and the median OS was 13.4 months (95% CI, 0–27.6). The most frequently mutated genes in afatinib-resistant patients were TP53 (44%) and EGFR (33%). Three afatinib-resistant patients harbored secondary HER2 alterations.ConclusionsOur results suggest that afatinib has a promising anti-tumor activity in patients with NSCLC harboring HER2 alterations. To our knowledge, this is the largest retrospective study about the clinical activity of afatinib in NSCLC patients with HER2 alterations.

show abstract

Section: Discussionmentioning

confidence: 87%

Efficacy and Resistance of Afatinib in Chinese Non-Small Cell Lung Cancer Patients With HER2 Alterations: A Multicenter Retrospective Study

Song

Chen³

et al. 2021

Front. Oncol.

Self Cite

View full text Add to dashboard Cite

show abstract

“…Interestingly, afatinib showed efficacy in a patient with squamous NSCLC harbouring a rare HER2 R896G mutation, with a PFS of >14 months. 57 Patients were mostly classified as VeriStrat 'Good' (412 patients, 61%) and in this patient subgroup, treatment with afatinib also led to an improvement in OS (HR 0.79 [95% CI 0.63-0.98]). 54…”

Section: Afatinib Outcomes In Squamous Non-small Cell Lung Cancer With Erbb Pathway Dysregulationmentioning

confidence: 99%

Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in the Treatment of Patients with Non-small Cell Lung Cancer of Squamous Histology: Focus on Afatinib

Reguart¹,

Reyes²

2021

Oncology &Amp; Haematology

View full text Add to dashboard Cite

“…00325 Meanwhile, other mutations of HER2 are very rare, which was only reported in sporadic cases. 14,15 Insertions and deletions (indels) in the kinase domain have been identified in EGFR family members including EGFR and HER2 as important cancer driver mutations. The most common indels were EGFR exon 19 deletions in NSCLC.…”

Section: Associated Content Data Supplementmentioning

confidence: 99%

“…13 Meanwhile, other mutations of HER2 are very rare, which was only reported in sporadic cases. 14,15…”

Section: Introductionmentioning

confidence: 99%

Identification of Recurrent Insertions and Deletions in Exon 18 and 19 of Human Epidermal Growth Factor Receptor 2 as Potential Drivers in Non–Small-Cell Lung Cancer and Other Cancer Types

Yin

Song

Shi

et al. 2022

JCO Precision Oncology

View full text Add to dashboard Cite

PURPOSE Human epidermal growth factor receptor 2 (HER2) belongs to the same family as epidermal growth factor receptor (EGFR) and is known as an important cancer driver gene. Insertions and deletions (indels) are frequent driver mutations in both EGFR and HER2. The most common HER2 indels are the exon 20 insertions within the kinase domain, while others are rarely reported. Our study aimed to investigate other indels of HER2 that may act as driver mutations in Chinese patients with different cancer types. METHODS In this retrospective study, patient samples were subjected to targeted sequencing covering HER2 and other cancer-related genes. Mutation profiles of patients harboring HER2 exon 18/19 indels were described. Identified HER2 exon 18/19 indels in our study were compared with external data from COSMIC. In silico and in vitro analyses were performed on selected indels of HER2 exon 18 and 19, respectively. RESULTS A total of 25 indels in HER2 exon 18/19, 17 of which being recurrent, were identified in 20 of 53,591 patients with lung cancer (0.037%), two of 5,888 patients with colorectal cancer (0.034%), two of 3,774 patients with breast cancer (0.053%), and one of 14 patients with urothelial carcinoma of the renal pelvis (7.1%). Most patients harboring HER2 exon 18/19 indels were absent of known driver mutations. In lung cancer, mutation profiles were comparable between patients carrying HER2 exon 18/19 indels and the two established HER2 drivers (exon 20 insertions and S310 mutations). The in silico and in vitro analyses suggested an activated state conferred by HER2 exon 18/19 indels, which could be targeted by different tyrosine kinase inhibitors. CONCLUSION Our study revealed a class of rare but unique indels in HER2 exon 18/19, which may act as driver mutations in several cancer types.

show abstract

<p>Response to Afatinib in a Patient with Non-Small Cell Lung Cancer Harboring HER2 R896G Mutation: A Case Report</p>

Cited by 6 publications

References 32 publications

Efficacy and Resistance of Afatinib in Chinese Non-Small Cell Lung Cancer Patients With HER2 Alterations: A Multicenter Retrospective Study

Efficacy and Resistance of Afatinib in Chinese Non-Small Cell Lung Cancer Patients With HER2 Alterations: A Multicenter Retrospective Study

Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in the Treatment of Patients with Non-small Cell Lung Cancer of Squamous Histology: Focus on Afatinib

Identification of Recurrent Insertions and Deletions in Exon 18 and 19 of Human Epidermal Growth Factor Receptor 2 as Potential Drivers in Non–Small-Cell Lung Cancer and Other Cancer Types

Contact Info

Product

Resources

About