Case Report: Afatinib Sensitivity in Rare EGFR E746_L747delinsIP Mutated LUAD With Peritoneal Metastases

Abstract

Patients with non-small cell lung cancer harboring the epidermal growth factor receptor (EGFR)-sensitive mutations are known to benefit significantly from EGFR tyrosine kinase inhibitors (TKIs), such as erlotinib, gefitinib, icotinib, or afatinib. However, the efficacy of EGFR-TKIs against rare mutations has not yet been well investigated. Here, we report a female patient with advanced lung adenocarcinoma (LUAD), carrying a rare mutation of EGFR Exon19 E746_L747delinsIP, who was administered first-generation EGFR-TKIs as the first-line treatment. The patient continued to progress slowly until peritoneal metastases have occurred. Subsequently, the patient was treated with anlotinib for 5 months until disease progression. Given the finding of the same EGFR rare mutation in peritoneal effusion without other EGFR-TKI resistance mutations, the patient received afatinib with a tremendous response. Our results may be of clinical relevance for patients with LUAD carrying this rare mutation, and these findings warrant further investigation.

Afatinib for the Treatment of NSCLC with Uncommon EGFR Mutations: A Narrative Review

“…Afatinib showed a median PFS of 11.97 months in a Taiwanese study on 5 patients suffering from stage IV lung adenocarcinoma and who had the EGFR L747P or L747S mutation, particularly in comparison to only 0.92 months with a first-generation EGFR-TKI ( p = 0.012), further illustrating the drug’s ability to treat these uncommon mutations [ 25 ]. Additionally, a patient with the E746_L747delinsIP mutation achieved partial remission (PR) and 7 months of PFS after receiving afatinib as fourth-line therapy [ 26 ]. Another case report showed that a patient with recurrent IV postoperative lung adenocarcinoma progressed again with multiple lines of treatment, including gefitinib, radiotherapy, and immunotherapy, and genetic testing was performed suggesting EGFR L858R and L747V mutations, and a 1-year PFS was obtained after treatment with afatinib [ 27 ].…”

PLEK2 promotes lung adenocarcinoma progression via activating the PI3K/AKT signaling pathway through SPC25 Running title: PLEK2 promotes LUAD via SPC25/PI3K/AKT axis

“…Current treatments for LUAD patients in early-stage include surgery in combination with postoperative radiotherapy, but most LUAD patients are diagnosed at an advanced stage [5]. In recent decades, advances in molecular pathogenesis of LUAD have allowed a variety of drugs to be available as molecular targeting reagents, including ge tinib, afatinib, erlotinib and osimertinib for inoperable patients [6,7]. Unfortunately, these novel targeting drugs bene t only a small subset of LUAD patients due to the speci c mutations and the development of drug resistance [8].…”