Advances in the Diagnosis and Treatment of Advanced Non-Small-Cell Lung Cancer With EGFR Exon 20 Insertion Mutation.

The discovery of epidermal growth factor receptor (EGFR) mutations has greatly changed the clinical outlook for patients with advanced non-small-cell lung cancer (NSCLC). Unlike the most common EGFR mutations, such as exon 19 deletion (del19) and exon 21 L858R point mutation, EGFR exon 20 insertion mutation (EGFR ex20ins) is a rare mutation of EGFR. Due to its structural specificity, it exhibits primary resistance to traditional epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), leading to poor overall survival prognosis for patients. In recent years, there has been continuous progress in the development of new drugs targeting EGFR ex20ins, bringing new hope for the treatment of this patient population. In this regard, we conducted a systematic review of the molecular characteristics, diagnostic advances, and treatment status of EGFR ex20ins. We summarized the latest data on relevant drug development and clinical research, aiming to provide reference for clinical diagnosis, treatment, and drug development.

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

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.

Therapeutic Advances of Rare ALK Fusions in Non-Small Cell Lung Cancer.

Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancer cases and is the leading cause of cancer-related death. Despite advances in chemotherapy and immunotherapy, the prognosis for advanced patients remains poor. The discovery of oncogenic driver mutations, such as anaplastic lymphoma kinase (ALK) mutations, means that a subset of patients has opportunities for targeted therapy. With the improvement of genetic testing coverage, more and more ALK fusion subtypes and ALK partners have been discovered, and more than 90 rare ALK fusion subtypes have been found in NSCLC. However, unlike the common fusion, echinoderm microtubule-associated protein-like 4 (EML4)-ALK, some rare ALK fusions such as striatin (STRN)-ALK and huntingtin interacting protein 1 (HIP1)-ALK, etc., the large-scale clinical data related to its efficacy are still immature. The clinical application of ALK-tyrosine kinase inhibitors (ALK-TKIs) mainly depends on the positivity of the ALK gene, regardless of the molecular characteristics of the fusion partner. Recent clinical studies in the ALK-positive NSCLC population have demonstrated differences in progression-free survival (PFS) among patients based on different ALK fusion subtypes. This article will introduce the biological characteristics of ALK fusion kinase and common detection methods of ALK fusion and focus on summarizing the differential responses of several rare ALK fusions to ALK-TKIs, and propose corresponding treatment strategies, so as to better guide the application of ALK-TKIs in rare ALK fusion population.