Efficacy generated by afatinib in a lung adenocarcinoma patient harboring HER2 S310Y mutation

Wang, Jian; Wen, Yuanyuan; Ding, Guanggui; Ding, Pan; Zhang, Lu; Liu, Jing; Zhang, Tengfei; Yang, Lin

doi:10.1080/15384047.2018.1449611

Cited by 9 publications

(8 citation statements)

References 22 publications

(19 reference statements)

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“…21 Besides of HER2 exon 20 insertion mutations, case-reports also demonstrated the efficacy of afatinib in NSCLC patients harboring HER2 point mutations like G776L, N813D, G660R, V659E and S310Y, regardless of the mutation domain (kinase domain, transmembrane domain or extracellular domain). 16,[22][23][24][25] These results show promising efficacy of afatinib in NSCLC patients harboring HER2 point mutations. However, the efficacy of afatinib in other rare HER2 mutations have been not explored.…”

Section: Introductionmentioning

confidence: 67%

“…11 Besides, some mutations in HER2 kinase domain are also documented, such as L755P, V773M, G776L E812K, N813D, R814H and Q828R. 14,22,27 Though rarely occurring, the mutations in transmembrane domain (G660R and V659E) 23 and extracellular domain (S310Y) 24,25 have also been identified. To the best of our knowledge, HER2 exon 22 R896G mutation has never been identified and reported.…”

Section: Discussionmentioning

confidence: 99%

“…Afatinib, an oral ErbB family blocker, has been reported to display promising results in NSCLC with HER2 mutations, including A775_G776insYVMA, P780_Y781ins GSP, G776L and N813D. 16,17,22 A few cases suggested that the patients with NSCLC harboring the mutations in transmembrane domain (G660R and V659E) 23,29 and extracellular domain (S310Y) 24,25 also can generate clinical benefit from afatinib therapy. In our case, a similar promising result and manageable toxicity profile were observed.…”

Section: Discussionmentioning

confidence: 99%

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

Yan³

et al. 2019

OTT

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Purpose: HER2 mutations are identified in approximately 2% of non-small-cell lung cancer (NSCLC) cases; however, until now, there are no approved standard targeted therapy for NSCLC patients harboring HER2 mutations. Case presentation: We present a 63-year-old male with a long smoking history, who was diagnosed with stage IV squamous cell lung cancer. After the failures of two lines of treatment with carboplatin plus gemcitabine and nidaplatin plus docetaxel, in turn, the patient received a next-generation sequencing of circulating tumor DNA to seek for potential treatment opportunities. A HER2 R896G mutation was identified with an allelic fraction of 50.77%. The patient received afatinib 40 mg a day and reached a partial response after two months of treatment. The progression-free survival was more than 14 months and the treatment of afatinib was ongoing. During the treatment, treatment-related paronychia and stomatitis occurred and relieved without any management. Conclusion: This is the first case report describing a NSCLC patient harboring a rare HER2 R896G mutation who responds to afatinib. This case suggests that afatinib might be efficacious in NSCLC patients harboring HER2 R896G mutations, and these results need to be further studied in prospective clinical trials.

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Section: Introductionmentioning

confidence: 67%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

Yan³

et al. 2019

OTT

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“…Moreover, the presence of HER2 mutation on top of HER2 amplification as resistance mechanism has not been reported before to our knowledge. Interestingly, the observed HER2 mutation is not the common HER2 exon 20 insertion, but an activating point mutation in the extracellular domain, that has been confirmed to be oncogenic both in vitro and in vivo [2, 3, 4].…”

Section: Discussionmentioning

confidence: 99%

Triple Trouble: A Case of Multiple Resistance Mechanisms after First Generation EGFR-TKI in NSCLC

et al. 2019

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Epidermal growth factor receptor (EGFR)-targeted therapy has become standard of care in advanced stages EGFR-mutant non-small cell lung cancer. Acquired resistance to first-line EGFR-tyrosine kinase inhibitor (TKI) and subsequent disease progression is a common problem and mostly due to a secondary mutation (T790M) in EGFR. We report a case of a patient with EGFR-mutated lung adenocarcinoma who developed a complex resistance profile: T790M mutation, HER2 mutation and HER2 amplification after first-line EGFR-TKI. This patient was safely treated with a combination of osimertinib and trastuzumab and achieved a clinically meaningful and clear molecular response.This is the first reported case of acquired resistance to first-line EGFR-TKI based on three resistance mechanisms, treated with molecular targeted combination therapy.

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“…Both mutations appear to have a homologous effect. Of the two, S310F has been most studied in different tumor tissues (both HER2-positive breast and HER2-negative lobular breast, lung, colorectal, ovarian, bladder, micropapillary urothelial, and endometrial) [29,33,54,[68][69][70] while S310Y has been more commonly associated with pulmonary adenocarcinoma while it has been also found in HER2-positive and HER2-negative breast cancer [29,33,55,71]. e fact that mutations in this position are present in different cancers suggests it could be an oncogenic mutation [72].…”

Section: Mutations In the Extracellular Domainmentioning

confidence: 99%

Somatic Mutations in HER2 and Implications for Current Treatment Paradigms in HER2-Positive Breast Cancer

Gaibar

Beltrán

Romero‐Lorca

et al. 2020

Journal of Oncology

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In one of every four or five cases of breast cancer, the human epidermal growth factor receptor-2 (HER2) gene is overexpressed. These carcinomas are known as HER2-positive. HER2 overexpression is linked to an aggressive phenotype and a lower rate of disease-free and overall survival. Drugs such as trastuzumab, pertuzumab, lapatinib, neratinib, and the more recent afatinib target the deregulation of HER2 expression. Some authors have attributed somatic mutations in HER2, a role in resistance to anti-HER2 therapy as differential regulation of HER2 has been observed among patients. Recently, studies in metastatic ER + tumors suggest that some HER2 mutations emerge as a mechanism of acquired resistance to endocrine therapy. In an effort to identify possible biomarkers of the efficacy of anti-HER2 therapy, we here review the known single-nucleotide polymorphisms (SNPs) of the HER2 gene found in HER2-positive breast cancer patients and their relationship with clinical outcomes. Information was recompiled on 11 somatic HER2 SNPs. Seven polymorphisms are located in the tyrosine kinase domain region of the gene contrasting with the low number of mutations found in extracellular and transmembrane areas. HER2-positive patients carrying S310F, S310Y, R678Q, D769H, or I767M mutations seem good candidates for anti-HER2 therapy as they show favorable outcomes and a good response to current pharmacological treatments. Carrying the L755S or D769Y mutation could also confer benefits when receiving neratinib or afatinib. By contrast, patients with mutations L755S, V842I, K753I, or D769Y do not seem to benefit from trastuzumab. Resistance to lapatinib has been reported in patients with L755S, V842I, and K753I. These data suggest that exploring HER2 SNPs in each patient could help individualize anti-HER2 therapies. Advances in our understanding of the genetics of the HER2 gene and its relations with the efficacy of anti-HER2 treatments are needed to improve the outcomes of patients with this aggressive breast cancer.

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Efficacy generated by afatinib in a lung adenocarcinoma patient harboring HER2 S310Y mutation

Cited by 9 publications

References 22 publications

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

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

Triple Trouble: A Case of Multiple Resistance Mechanisms after First Generation EGFR-TKI in NSCLC

Somatic Mutations in HER2 and Implications for Current Treatment Paradigms in HER2-Positive Breast Cancer

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