Tyrosine kinase inhibitors (TKIs) that block EGFR are effective treatments for many cases of advanced non-small cell lung cancer (NSCLC), but are limited by the fact that patients will eventually develop resistance against them. Overexpression of the MET gene may contribute to EGFR-TKI resistance, suggesting that combined inhibition of both EGFR and MET may prevent or overcome this drug resistance. Several MET inhibitors have been developed, including cabozantinib (Cometriq), tivantinib, onartuzumab, and ficlatuzumab, and ongoing trials are investigating the safety and effectiveness of combining them with an EGFR-TKI like erlotinib (Tarceva) or gefitinib (Iressa).
Farletuzumab is an antibody (a type of immune system protein) that inhibits folate receptor α (FOLR1), a protein that is essential for cell proliferation. FOLR1 is overexpressed in a number of tumor types, including non-small cell lung cancer (NSCLC) and, especially, adenocarcinoma. Farletuzumab reduced tumor growth in animal models of cancer, and was well-tolerated in phase I and II studies. An ongoing phase II study is evaluating the effectiveness of combining farletuzumab treatment with chemotherapy in patients with advanced lung adenocarcinoma.
Conatumumab is an antibody (a type of immune system protein) that targets TR-2, a protein that is expressed in tumor tissue in a variety of cancer types. A phase II study of patients with previously untreated advanced non-small cell lung cancer (NSCLC) receiving either conatumumab or placebo in combination with standard paclitaxel (Taxol)–carboplatin (Paraplatin) chemotherapy showed that conatumumab was well tolerated, but did not improve clinical outcomes. However, it is possible that, in patients selected for relevant biomarkers, conatumumab may show effectiveness that is not seen in an unselected patient population.
A review of recent research discusses EGFR inhibition in the treatment of non-small cell lung cancer (NSCLC). Blocking EGFR using drugs called EGFR-tyrosine kinase inhibitors (TKIs) is an effective treatment for advanced NSCLC in patients with mutations in the EGFR gene. However, chemotherapy remains the standard of care for advanced NSCLC without EGFR mutations. Unfortunately, patients commonly develop drug resistance to TKIs like erlotinib (Tarceva) or gefitinib (Iressa). Newer TKIs like afatinib, which target multiple proteins and irreversibly inhibit them, are being explored in clinical trials and may be effective in patients who have become resistant to first-generation TKIs.
A promising new drug for a subtype of non-small cell lung cancer (NSCLC) was recently granted priority review status by the U.S. Food and Drug Administration (FDA). If approved, afatinib would be the first drug on the market specifically for treating advanced or metastatic NSCLC associated with epidermal growth factor receptor (EGFR) mutations. Continue reading…