Afatinib as first‐line treatment for advanced lung adenocarcinoma patients harboring <i>HER2</i> mutation: A case report and review of the literature

Shi, Yuequan; Wang, Mengzhao

doi:10.1111/1759-7714.12906

Cited by 15 publications

(11 citation statements)

References 34 publications

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“…This might indicate that ERBB2 mutation was a poor prognostic factor. Although the previous case report showed that ERBB2 mutated NSCLC patient could benefit from afatinib treatment, a retrospective study in China suggested that compared with chemotherapy, afatinib was not more beneficial to ERBB2 mutated NSCLC patients . Also, most of the clinical trials, including afatinib, dacomitinib, and neratinib, focused on ERBB2 exon 20 insertion mutations and failed with a low objective response rate of 11%–19% .…”

Section: Discussionmentioning

confidence: 97%

Mutational landscape and characteristics of ERBB2 in non‐small cell lung cancer

et al. 2020

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Background: Tyrosine kinase domain (TKD) mutation and particularly exon 20 insertion mutations of ERBB2 have been extensively reported in non-small cell lung cancer (NSCLC). Due to the increased accessibility of next-generation sequencing, more ERBB2 mutations within the non-TKD can be detected in clinical practice. Nevertheless, the clinical significance of non-TKD mutations remains unknown. Hence, this study was designed to comprehensively outline the landscape and characteristics of ERBB2 mutations in NSCLC. Methods: A total of 1934 patients with NSCLC from cBioPortal were included in the study. An ERBB2 mutation cohort was identified, while subsequent analyses revealed clinical and genomic characteristics. Results: The frequency of ERBB2 mutation was 4.5%, and it was determined to be more likely to occur in never-smokers. ERBB2 mutations occurring in the non-TKD accounted for 57.5% of ERBB2 mutations. In the non-TKD, missense mutation was the most recurrent mutation type, and S310F was the most recurrent mutation variant. ERBB2 mutations within non-TKD also had a strong oncogenic ability where up to 37.5% of ERBB2 oncogenic mutations were within non-TKD. The co-mutation of EGFR or KRAS was higher in the non-TKD mutation compared to the TKD mutation. Shorter overall survival was observed in ERBB2-mutant patients compared with ERBB2 wild-type patients. There was no significant difference in overall survival between patients with non-TKD mutations and TKD mutations. Conclusions: The present study showed that a considerable portion of non-TKD mutations were oncogenic. ERBB2 mutation was a poor prognostic factor. The non-TKD mutation might also be used as a therapeutic target in ERBB2-directed target therapy. Key points • Significant findings of the study ERBB2 mutations were more abundant within a nontyrosine domain than those within the tyrosine domain. Up to 37.5% of ERBB2 oncogenic mutations were within the nontyrosine domain. ERBB2 mutation was a poor prognostic factor.• What this study adds The frequency of EGFR or KRAS co-mutations were significantly higher in ERBB2 mutations within the nontyrosine kinase domain compared to ERBB2 mutations within the tyrosine kinase domain. Nontyrosine domain mutations confer equal overall survival to tyrosine domain mutations.

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Section: Discussionmentioning

confidence: 97%

Mutational landscape and characteristics of ERBB2 in non‐small cell lung cancer

et al. 2020

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“…All four responders harbored an exon 20 insertion and they were treated with Trastuzumab, Afatinib or TDM-1 (Chuang, et al, 2017). In a recent case report, a patient with the recurrent YVMA insertion treated with Afatinib first-line achieved a PR that lasted 12 months (Shi & Wang, 2018). Another group reported the case of a woman with NSCLC harboring a HER2 exon 20 mutation (c.2437A>G) who previously failed cytotoxic chemotherapy and Gefitinib treatment but responded to Afatinib .…”

Section: Clinical Responses In Her2 Mutant Lung Cancer Patients To Anmentioning

confidence: 99%

Prevalence and role of HER2 mutations in cancer

Cocco

Lopez

Santin

et al. 2019

Pharmacology & Therapeutics

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HER2 activating mutations act as oncogenic drivers in various cancer types. In the clinic, they can be identified by next generation sequencing (NGS) in either tumor biopsies or circulating cell-free DNA (cfDNA). Preclinical data indicate that HER2 "hot spot" mutations are constitutively active, have transforming capacity in vitro and in vivo and show variable sensitivity to anti-HER2 based therapies. Recent clinical trials also revealed activity of HER2-targeted drugs against a variety of tumors harboring HER2 mutations. Here, we review the prevalence and type of HER2 mutations identified in different human cancers, their biochemical and biological characterization, and their sensitivity to anti HER2-based therapies in both preclinical and clinical settings.

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“…The first case is an account of a never-smoking female with a HER2 V659E mutation who had a confirmed PR for 5 months, and the second case described a female never-smoker with a HER2 pG776delinsVC who achieved a PR for 12þ months. 6,7 No other TKIs have been evaluated in the first-line setting. In a basket trial of ado-trastuzumab, 2 of 3 untreated patients enrolled achieved a PR.…”

Section: Discussionmentioning

confidence: 99%