The effectiveness of afatinib in patients with lung adenocarcinoma harboring complex epidermal growth factor receptor mutation

Wu, Shang‐Gin; Yu, Chong‐Jen; Yang, James Chih‐Hsin; Shih, Jin‐Yuan

doi:10.1177/1758835920946156

Cited by 19 publications

(29 citation statements)

References 69 publications

(101 reference statements)

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“…In a retrospective study focusing on compound mutations, 125 NSCLC patients with these alterations, excluding de novo exon 20 p.T790M compounds, received an EGFR TKI as first-line treatment [ 47 ]. Overall, treatment with afatinib showed longer PFS than gefitinib and erlotinib, and longer OS than erlotinib.…”

Section: Resultsmentioning

confidence: 99%

“…In cases of compound common EGFR mutations, no difference was observed among the three drugs in terms of response (RR: gefitinib 83%, erlotinib 73.7%, afatinib 88.2%) and PFS (gefitinib 10.9, erlotinib 8.5, afatinib 9.6 months, p = 0.385). Conversely, afatinib demonstrated higher RR and prolonged PFS in those patients with combined uncommon pattern (RR: afatinib 78.9%, gefitinib 38.9%, erlotinib 20%, p = 0.013; PFS: afatinib 10.5, gefitinib 3, erlotinib 0.9 months) [ 47 ] ( Figure 3 ).…”

Section: Resultsmentioning

confidence: 99%

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Uncommon EGFR Compound Mutations in Non-Small Cell Lung Cancer (NSCLC): A Systematic Review of Available Evidence

et al. 2022

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Compound epidermal growth factor receptor (EGFR) mutations represent a heterogeneous subgroup of non-small cell lung cancer (NSCLC) patients with uncommon EGFR mutations. We conducted a systematic review to investigate the available data on this patients’ subgroup. Overall, we found a high heterogeneity in the incidence of compound mutations (4–26% of total EGFR mutant cases), which is dependent on the different testing methods adopted and the specific mutations considered. In addition, the relative incidence of distinct compound subclasses identified is reported with extreme variability in different studies. Preclinical and clinical data, excluding de novoEGFR exon 20 p.T790M compound mutations, show good responses with EGFR tyrosine kinase inhibitors (TKIs) (combined common mutations: response rate (RR) ≥ 75% with either first- or second-generation TKIs; combined common plus uncommon: RR 40–80% and 100% with first-generation TKIs and afatinib, respectively; combined uncommon: RR 20–70%, ~80% and ~75% with first-generation TKIs, afatinib and osimertinib, respectively). Overall, data are consistent in supporting the use of EGFR TKIs in treating compound EGFR mutations, taking into account different sensitivity profile of accompanying EGFR mutations for selecting the most adequate EGFR TKI for individual patients.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Uncommon EGFR Compound Mutations in Non-Small Cell Lung Cancer (NSCLC): A Systematic Review of Available Evidence

et al. 2022

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“…In both cases, K757N was found in combination with the classical EGFR sensitizing mutation L858R. In the case report by Wu et al [7], the patient had a transient, stable response to TKI therapy with gefitinib for 8.8 months before progression. The other reported case also received gefitinib for 12.4 months before progression [8].…”

Section: Discussion/conclusionmentioning

confidence: 94%

Complex Germline K757N Mutation in Non-Small-Cell Lung Cancer: A Case Report

2022

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Epidermal growth factor receptor (EGFR) mutations are usually oncogenic drivers of lung tumor development and progression. While common sensitizing mutations respond well to targeted therapy, the relevance of germline EGFR mutations is less clear. We describe a 65-year-old, previously healthy, male diagnosed with non-small-cell lung cancer. Familial history for lung cancer is negative. Targeted next-generation sequencing on the tumor biopsy sample revealed an atypical EGFR K757N mutation at 50% allele frequency and genetic review of a previously acquired gastric sample confirms the mutation as a germline change. He received standard first-line chemoimmunotherapy with carboplatin, pemetrexed, and pembrolizumab, and after 8 months therapy continues, with stable disease, to receive maintenance pemetrexed and pembrolizumab. To our knowledge, this is the first report of an atypical, germline K757N EGFR mutation. While the clinical relevance of this mutation is unclear, standard reporting of the allelic frequency of novel, atypical mutations can detect potential germline changes.

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“…In line with our observation, a pooled analysis revealed that afatinib resulted in an objective response rate (ORR) of 77.1% and a median time to treatment failure (TTF) of 14.7 mo [95% confidence interval (CI): 6.8-18.5 mo] in EGFR TKI–naive patients harboring compound mutations[ 6 ]. A recent retrospective study also shows that afatinib is associated with a more favorable PFS compared with gefitinib [hazard ratio (HR) = 2.01; 95%CI: 1.11-3.62] and erlotinib [HR = 2.61; 95%CI: 1.31-5.22] in patients with EGFR compound mutations[ 7 ]. Especially in those with uncommon patterns (without 19 deletion and L858R), afatinib yielded a higher response rate (afatinib vs gefitinib vs erlotinib: 78.9% vs 38.9% vs 20.0%, P = 0.013) and significantly longer PFS (afatinib vs gefitinib vs erlotinib: 10.5 mo vs 3.0 mo vs 0.9 mo).…”

Section: Discussionmentioning

confidence: 99%

Non-small-cell lung cancer with epidermal growth factor receptor L861Q-L833F compound mutation benefits from both afatinib and osimertinib: A case report

Zhang

Shen

et al. 2021

WJCC

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BACKGROUND Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have been adopted as the standard of care for non-small cell lung cancer (NSCLC) patients harboring EGFR sensitizing mutations. Besides the two common mutations exon 19 deletion and L858R, which together comprise approximately 85% of EGFR mutations in NSCLC, rare EGFR mutations also exist, including point mutations, deletions, and insertions spanning EGFR exons 18-25. However, the responsiveness of uncommon EGFR mutations to EGFR TKIs remains elusive and attracts increasing interest. CASE SUMMARY Herein, we report a 55-year-old male patient with stage IV NSCLC harboring a rare EGFR L833F-L861Q compound mutation in cis . The patient achieved a partial response to first-line treatment with afatinib and a progression-free survival of 10 mo. After afatinib failure, the patient received multiple line treatments with chemotherapy. Upon disease progression, the heavily pretreated patient was treated with osimertinib and bevacizumab, and both lung lesion and brain metastases were stable for more than 3 mo. He had an overall survival of 25 mo. CONCLUSION Our case revealed that both afatinib and the osimertinib + bevacizumab combination demonstrated clinical efficacy in NSCLC harboring an EGFR L833F-L861Q compound mutation. The results provide more therapeutic options for patients with rare compound mutations.

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The effectiveness of afatinib in patients with lung adenocarcinoma harboring complex epidermal growth factor receptor mutation

Cited by 19 publications

References 69 publications

Uncommon EGFR Compound Mutations in Non-Small Cell Lung Cancer (NSCLC): A Systematic Review of Available Evidence

Uncommon EGFR Compound Mutations in Non-Small Cell Lung Cancer (NSCLC): A Systematic Review of Available Evidence

Complex Germline K757N Mutation in Non-Small-Cell Lung Cancer: A Case Report

Non-small-cell lung cancer with epidermal growth factor receptor L861Q-L833F compound mutation benefits from both afatinib and osimertinib: A case report

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