A large phase III study has found that the targeted therapy cetuximab (Erbitux), combined with platinum-based chemotherapy, is effective as a first-line treatment for patients with advanced non–small-cell lung cancer (NSCLC). This is the first time a targeted drug has shown a survival benefit as a first-line treatment for patients with NSCLC, including all subtypes of the disease, reported lead author Robert Pirker, md, associate professor of medicine at Medical University of Vienna in Austria at the ASCO meeting (abstract 3).
“Patients with advanced NSCLC have limited treatment options and life expectancy is short, so the survival increase shown in this study is an important step for these patients” said Dr. Pirker. For patients with the most advanced form of NSCLC, 1-year survival is about 30% and 5-year survival is just 1% to 2%. “These results clearly establish cetuximab in combination with chemotherapy as a new standard in first-line treatment of NSCLC.”
This study evaluated the addition of the epidermal growth factor receptor (EGFR) antibody cetuximab to platinum-based chemotherapy (cisplatin and vinorelbine). The current standard of care for newly diagnosed patients with advanced NSCLC is platinum (either cisplatin or carboplatin) combined with a “third-generation drug” (vinorelbine, gemcitabine [Gemzar], paclitaxel, or docetaxel [Taxotere]). Earlier studies of different EGFR-targeted drugs, such as the tyrosine kinase inhibitors gefitinib (Iressa) and erlotinib (Tarceva), did not show an additional benefit over first-line standard chemotherapy and are currently approved for patients whose initial chemotherapy has failed.
In this study, 1,125 patients in 30 countries were randomized to receive either chemotherapy alone (568) or chemotherapy plus cetuximab (557); 94% had stage IV disease (meaning the cancer had spread to other parts of the body). Overall survival was higher for those who received cetuximab plus chemotherapy (11.3 months) compared to those receiving chemotherapy alone (10.1 months). Also, the response rate was better in the chemotherapy plus cetuximab arm (36.3%) vs chemotherapy alone (29.2%).
The benefit of cetuximab was seen in patients with all histologic subtypes of NSCLC, including adenocarcinoma and squamous cell carcinoma, the two most common subtypes. Other targeted therapies for lung cancer have only proven effective against certain subtypes.
As expected, the most frequent side effect was an acne-like rash, which was manageable with medication. Moderate rashes were seen more frequently in patients receiving cetuximab (10.4%) than in patients receiving chemotherapy alone (0.2%).
The authors state that based on these findings, there will be more studies evaluating cetuximab in earlier stages of the disease, such as in combination with chemotherapy or chemoradiotherapy in patients with locally advanced disease or as an additional treatment after surgery in patients with early-stage disease.