<p>Second-generation EGFR and ErbB tyrosine kinase inhibitors as first-line treatments for non-small cell lung cancer</p>

Abstract

The discovery that mutations in the EGFR gene are present in up to 50% of patients with lung adenocarcinoma, and the development of highly efficacious EGFR tyrosine kinase inhibitors (TKIs), has revolutionized the way this common malignancy is treated. Three generations of EGFR TKIs are now approved for use in EGFR mutation-positive non-small cell lung cancer (NSCLC); the first-generation agents erlotinib, gefitinib, and icotinib; the second-generation ErbB family blockers afatinib and dacomitinib; and most recently, osimertinib, a third-generation EGFR TKI. The second-generation agents have demonstrated impressive efficacy relative to both standard platinum-based chemotherapy and first-generation EGFR TKIs, significantly improving response and progression-free and overall survival. Data from real-world studies suggest that afatinib is as effective and well tolerated in routine clinical practice as it is in clinical studies and is effective in patients with certain uncommon EGFR mutations, patients with brain metastases, and older patients. Few real-world data are available for dacomitinib in the first-line setting. Afatinib and dacomitinib have similar safety profiles, with acne/skin dryzness, diarrhea, stomatitis, and paronychia the most common adverse events (AEs) reported in clinical and real-world studies. Numerous studies have shown that tolerability-guided dose reductions can help manage afatinib-related AEs without reducing efficacy. As the number of therapeutic options for advanced NSCLC increases, the optimal choice for first-line treatment will be determined by considering patient factors such as the presence of brain metastases, the type of EGFR mutation, tolerability, and subsequent therapy options for long-term treatment.

Purpuric drug eruptions induced by EGFR tyrosine kinase inhibitors are associated with IQGAP1‐mediated increase in vascular permeability

“…Although gefitinib showed the most obvious inhibitory effect on the phosphorylation of EGFR and ERK of these EGFR‐TKIs, especially in HMVECs, erlotinib was selected for further experiments. This is because erlotinib is a more widely used first‐generation EGFR‐TKI in clinical conditions than gefitinib .…”

A comprehensive study on the oncogenic mutation and molecular pathology in Chinese lung adenocarcinoma patients

“…Several oncogenic drivers have been identified in lung adenocarcinoma, including mutations in the epidermal growth factor receptor (EGFR) [ 8 ], fusions of anaplastic lymphoma kinase (ALK) [ 9 ], and rearrangements of ROS proto-oncogene 1 receptor tyrosine kinase (ROS1) [ 10 ]. Accumulating evidence demonstrated that mutations of EGFR were identified in 15–30% of lung adenocarcinomas in Caucasians [ 11 ] and 40–60% in East Asians [ 12 – 14 ], indicating that the frequency of activated mutations of EGFR depends on ethnicity.…”

A new KIF5B–ERBB4 gene fusion in a lung adenocarcinoma patient

“…With respect to this finding, the MTB, based on scarce literature data and taking into account the lack of other validated efficient drugs in a fifth-line setting for NSCLC, suggested to offer the patient Afatinib treatment, a second generation pan-ErbB tyrosine kinase inhibitor, at 40mg/day, as already described in NSCLC with EGFR mutation 7 . This treatment had actually been reported to display some efficacy in a lung squamous cell carcinoma patient with a tumor missense mutation in the ERBB4 gene (p.Arg847His) 8 , and in an urothelial carcinoma patient with ERBB3 missense mutations 9 .…”