Genetic Ablation of Epidermal EGFR Reveals the Dynamic Origin of Adverse Effects of Anti-EGFR Therapy

“Cancer patients treated with anti-EGFR (epidermal growth factor receptor) drugs often develop a dose-limiting pruritic rash of unknown etiology. The aims of our study were to define causal associations from a clinical study of cutaneous and systemic changes in patients treated with gefitinib and use these to develop and characterize a mouse model that recapitulates the human skin rash syndrome caused by anti-EGFR therapy. We examined the patients’ plasma before and after treatment with gefitinib and documented changes in chemokines and leukocyte counts associated with the extent of rash or the presence of pruritus. We established a parallel mouse model by ablating EGFR in the epidermis. These mice developed skin lesions similar to the human rash. Before lesion development, we detected increased mRNA expression of chemokines in the skin associated with early infiltration of macrophages and mast cells and later infiltration of eosinophils, T cells, and neutrophils.”


VeriStrat Assay May Help Select NSCLC Patients for Second-Line Therapy

“VeriStrat, a serum-based protein assay, can help select which patients with non–small cell lung cancer (NSCLC) who are not known to have epidermal growth factor receptor (EGFR) mutations might benefit from an EGFR-targeted agent, according to a study described at the 2013 Best of ASCO Los Angeles meeting by Heather A. Wakelee, MD, Associate Professor of Medicine, Stanford University, Palo Alto, California.”


Funding Strategy Needed to Support EGFR Mutation Testing in Canada

Funding represents a decisive barrier to the nationwide implementation of genetic testing for a key lung cancer mutation in Canada, a recent study finds. Patients with non-small cell lung cancer (NSCLC) who have a mutation in the EGFR gene frequently benefit from treatment with EGFR inhibitors. AstraZeneca, makers of the EGFR inhibitor gefinitinb (Iressa), reimbursed Canadian laboratories for offering EGFR mutation testing to patients with advanced non-squamous NSCLC for 12 months. EGFR mutation testing was rapidly adopted into routine clinical practice in Canada. However, testing rates dropped sharply once the reimbursement program ended. Researchers conclude that a national strategy is needed to provide resources for continued EGFR testing.


Afatinib is FDA-Approved: What It Means For NSCLC Patients


On July 12, the FDA announced that it had approved the targeted therapy afatinib (Gilotrif) for the treatment of metastatic non-small cell lung cancer (NSCLC) with mutations in the epidermal growth factor receptor (EGFR) gene.

EGFR mutations occur in about 10 to 15 percent of all NSCLC patients. The overexpression of the EGFR protein caused by the mutation leads to rapid cell division in tumors. Prior to the approval of afatinib, patients in the United States could only take erlotinib (Tarceva) to combat the EGFR mutation. The third major drug available to treat EGFR-mutated tumors, gefitinib (Iressa) has not yet been approved by the United States but is readily available in many other countries. Erlotinib has consistently outperformed gefitinib, so its lack of availability in the U.S. is no huge loss. Continue reading…


Patients with Drug-Resistant Lung Cancer Might Benefit from New Drug CO-1686

Patients with non-small cell lung cancer (NSCLC) who have mutations in the EGFR gene often improve significantly when treated with EGFR inhibitors like erlotinib (Tarceva) or gefitinib (Iressa). However, in virtually all cases, patients eventually develop resistance to these drugs. Resistance to EGFR inhibitors is frequently associated with patients developing an additional mutation in the EGFR gene called T790M. Hope for these patients may come from a new EGFR inhibitor designed to target the T790M mutation, called CO-1686. Preliminary results from an ongoing early clinical trial of CO-1686 show that the drug shrank tumors in at least a subset of patients with EGFR-mutant advanced NSCLC who were resistant to EGFR inhibitors and carried the T790M mutation.


Medical Societies Recommend Testing for Lung Cancer Biomarkers


New guidelines recommend lung cancer patients be genetically tested to determine whether they are amenable to a class of drugs called tyrosine kinase inhibitors. Patients with EGFR or ALK mutations could benefit more from such targeted therapies, and suffer fewer side effects, than with chemotherapy. Continue reading…


Testing for EGFR and ALK Mutations Recommended for All Lung Adenocarcinoma Patients

All patients with advanced adenocarcinoma of the lung, a type of non-small cell lung cancer (NSCLC), should be tested for mutations in the EGFR and ALK genes, according to guidelines developed by three prominent professional medical societies. Mutations in these genes predict a much higher likelihood of benefitting from treatment with EGFR inhibitors like erlotinib (Tarceva) and gefitinib (Iressa) o,r ALK inhibitors like crizotinib (Xalkori), respectively. The tests should be performed for all adenocarcinoma patients as soon as advanced disease is detected, regardless of the sex, race, smoking history, or other clinical risk factors.


Switching from Iressa to Tarceva Halts Drug-Induced Immune Suppression in Lung Cancer Patient

Neutropenia (a reduction in white blood cells) is a rare, but potentially serious side effect of the cancer drug gefitinib (Iressa). Iressa is used to treat non-small cell lung cancer (NSCLC) with mutations in the EGFR gene. A patient with EGFR-mutant advanced adenocarcinoma of the lung (a type of NSCLC) was treated with Iressa. Her tumor shrank, but she experienced severe neutropenia, leaving her at risk of dangerous infections. She was switched to erlotinib (Tarceva), another EGFR inhibitor, after which her neutropenia cleared up. The patient has since continued on Tarceva without neutropenia or cancer progression for over 9 months. This case suggests that Iressa-induced neutropenia can be safely treated by switching to Tarceva, although caution should be used in drawing conclusions from a single case study.


Zolinza May Circumvent TKI Resistance in Some Lung Cancer Patients

Tyrosine kinase inhibitors (TKIs) like erlotinib (Tarceva) and gefitinib (Iressa) are effective treatments for many patients with non-small cell lung cancer (NSCLC) who have mutations in the EGFR gene. However, patients who also have a certain version of the BIM gene are resistant to TKIs. Vorinostat (Zolinza), a member of a family of drugs called histone deacetylase (HDAC) inhibitors, restored the antitumor activity of Iressa in EGFR-mutant NSCLC cells and in animal models of EGFR-mutant NSCLC that carried the resistant BIM version. Combining Zolinza with TKIs may therefore help circumvent TKI resistance in patients who have the resistant form of BIM.