Clinical benefit from afatinib in an advanced squamous cell lung carcinoma patient harboring &lt;em&gt;HER2&lt;/em&gt; S310Y mutation: a case report

Gao, Yan; Ai-hong, Zheng; Zhu, Xiuming; Song, Jia; Xue, Qian

doi:10.2147/ott.s182812

Cited by 7 publications

(5 citation statements)

References 26 publications

(23 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: 69%

“…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

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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: 69%

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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“…For example, afatinib given after chemotherapy, antiangiogenesis therapy, and icotinib successfully stabilized EGFR and HER2 mutation-positive squamous cell lung cancer in an elderly Chinese patient for at least 8 months, with no treatment-related adverse events. 63 Further details have also been published of a patient enrolled in LUX-Lung 8, with multiple genetic aberrations, including EGFR copy number amplification and mutations in ErbB4, ALK, RET and BRCA. This patient experienced prolonged PFS (14.7 months) and OS (17.7 months) with afatinib; 64 of note, final analysis of LUX-Lung 8 has since identified 21 patients who remained on afatinib treatment for at least 12 months.…”

Section: Evidence From Individual Patient Casesmentioning

confidence: 99%

Advanced Squamous Cell Carcinoma of the Lung: Current Treatment Approaches and the Role of Afatinib

Santos

Hart

2020

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Options for the treatment of squamous cell lung carcinoma expanded in recent years with the introduction of the immune checkpoint inhibitors into routine clinical practice in both the first-and second-line settings but are still limited. As a result, pembrolizumab, given either alone or in combination with platinum-based chemotherapy, is now a standard first-line treatment for squamous cell lung cancer. However, few options exist once patients have progressed on immune checkpoint inhibitors and chemotherapy. In this setting, the irreversible ErbB family blocker, afatinib, has a potential role as second or subsequent therapy for some patients. The Phase III LUX-Lung 8 study demonstrated that afatinib significantly prolonged progression-free and overall survival compared with erlotinib in patients with squamous cell lung carcinoma. Notably, retrospective, ad-hoc biomarker analyses of a subset of patients from LUX-Lung 8 suggested that patients with ErbB family mutations derived particular benefit from afatinib, especially those with ErbB2 (HER2) mutations. Afatinib has a manageable and predictable safety profile, and adverse events can be managed with the use of a tolerability-guided dose modification protocol. Until more data are available, afatinib could be considered as a potential second-line treatment option for patients who have progressed on combined pembrolizumab and platinum-based chemotherapy and are ineligible for more established second-line options, or as a third-line option in patients who have received first-line immunotherapy, and second-line chemotherapy or chemotherapy and antiangiogenesis therapy. However, further data are required to support the use of afatinib following immunotherapy. Given that treatment options are limited in both of these settings, investigating an agent with an entirely new mechanism of action is warranted. If available, molecular analysis to identify ErbB family mutations or the use of proteomic profiling could help to further isolate patients who are likely to derive the most benefit from afatinib.

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Clinical benefit from afatinib in an advanced squamous cell lung carcinoma patient harboring <em>HER2</em> S310Y mutation: a case report

Cited by 7 publications

References 26 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

<p>Advanced Squamous Cell Carcinoma of the Lung: Current Treatment Approaches and the Role of Afatinib</p>

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