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.
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…
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.
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.
Neutropenia is a rare side effect of gefitinib and was scarcely reported in many large-scale randomized phase III trials using gefitinib monotherapy as first-line treatment. Clinicians should be aware that gefitinib-induced neutropenia in patients with non-small cell lung cancer can be treated successful by switching to erlotinib.
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.
Non-small cell lung cancer (NSCLC) patients with mutations in the EGFR gene are likely to benefit from treatment with tyrosine kinase inhibitors (TKIs) like erlotinib (Tarceva) and gefitinib (Iressa), while KRAS mutations predict poor TKI response. A study of patients who were not taking TKIs and had stages I/II/III NSCLC that had been surgically removed found no difference in recurrence or survival between patients with or without EGFR or KRAS mutations. This finding suggests that, while EGFR and KRAS mutations are useful for identifying patients who may benefit from targeted treatments like TKIs, they do not predict overall clinical outcomes by themselves.