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

Abstract

Afatinib, the world’s first irreversible ErbB family (containing four different cancer cell epidermal growth factor receptors, including EGFR, HER2, ErbB3, and ErbB4) inhibitor, is a second-generation oral epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). It can be used as a first-line treatment for locally advanced or metastatic non-small-cell lung cancer (NSCLC) with an EGFR-sensitive mutation or for patients with locally advanced or metastatic squamous lung cancer whose disease progresses during or after platinum-containing chemotherapy. Currently, with the use of third-generation EGFR-TKIs, afatinib is no longer clinically indicated as the first choice for patients with NSCLC who have EGFR-sensitive mutations. However, afatinib showed a considerable inhibitory effect in NSCLC patients with uncommon EGFR mutations (G719X, S768I, and L861Q) according to a combined post hoc analysis of the LUX-Lung2/3/6 trials. With the development of genetic testing technology, the detection rate of uncommon EGFR mutations is increasing. The aim of this paper is to describe in detail the sensitivity of rare EGFR mutations to afatinib and to provide information and a reference for those suffering from advanced NSCLC who have uncommon EGFR mutations.

Metabolomic, microbiome and transcriptomic study of crofelemer or loperamide in rat model of afatinib-induced intestine epithelial damage and diarrhea

“…Several large randomized controlled trials and real world studies support the use of afatinib in unresectable late stage or metastatic lung cancer. Except for NSCLC patients harboring common or rare EGFR mutations, afatinib has also shown potential efficacy in treating those with NRG1 fusions (Lu et al, 2021;Jiang et al, 2023;Laskin et al, 2020). Diarrhea has been a common adverse effect in multiple clinical trials for afatinib.…”