Forty patients with non-small cell lung cancer (NSCLC) with brain metastases (cancer that had spread to the brain) were treated with the EGFR inhibitor Tarceva (erlotinib) and whole-brain radiation therapy (WBRT). Tarceva plus WBRT was relatively well tolerated and resulted in median survival rates (10.9 months) that were higher than in a previous trial of WBRT alone (3.9 months). The fact that many NSCLC patients carry mutations in the EGFR gene may contribute to the beneficial effects of adding Tarceva treatment to WBRT in NSCLC with brain metastases.
A review of recent research discusses EGFR inhibition in the treatment of lung cancer. Scientists have now demonstrated that EGFR-tyrosine kinase inhibitors (TKIs), either by themselves or combined with chemotherapy, are effective first-line treatments for advanced non-small cell lung cancer (NSCLC) with EGFR mutations, and as second-line or maintenance treatments for all advanced NSCLC. TKIs like erlotinib (Tarceva) or gefitinib (Iressa), or anti-EGFR antibodies like cetuximab (Erbitux), may also enhance the effectiveness of radiation therapy for locally advanced NSCLC. Other biomarkers, such as KRAS mutations, may also help predict response to EGFR inhibition therapy.
Erlotinib (Tarceva) was recently approved in the EU as a first-line treatment for advanced non-small cell lung cancer (NSCLC) in patients with mutations in the EGFR gene. In these patients, this recently published guide explains, Tarceva is better tolerated than standard chemotherapy, has higher treatment response rates, and results in longer time periods without the cancer worsening. However, Tarceva does not benefit patients without EGFR mutations, its effect on overall survival has not yet been clearly determined and the risk of serious side effects requires careful patient monitoring.
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.
In a recent phase I/IIA study, patients with extensive-stage small-cell lung cancer (SCLC) that had not previously been treated were given a drug called pomalidomide. The pomalidomide treatment was combined with standard chemotherapy consisting of cisplatin (Platinol) and etoposide (Etopophos/Toposar). Pomalidomide appeared to be safe, with a maximum tolerated dose of 4 mg per day. However, it did not appear to increase the efficacy or decrease the toxicity of the chemotherapy.
VeriStrat® is a blood test for advanced non-small cell lung cancer (NSCLC) patients intended to determine whether the patients would benefit from erlotinib (Tarceva) treatment. A retrospective analysis of blood samples from elderly patients (age 70+ yr) with advanced NSCLC who had been treated with either Tarceva, gemcitabine (Gemzar), or both found that patients with a “good” VeriStrat result had better outcomes than those with a “poor” result when given Tarceva either alone or in combination with Gemzar, while the benefits of Gemzar alone were unaffected by VeriStrat status. The study authors conclude that elderly patients with poor VeriStrat results should be treated with Gemzar, while first-line Tarceva treatment may be appropriate for patients with good Veristrat results.