KRAS mutations occur in 30% of patients with non-small cell lung cancer, especially adenocarcinoma. For long time KRAS mutation has been related with poor prognosis and poor response to chemotherapy. Recent data however show that this is both not true. It seems that response, progression free survival and overall survival is similar in KRAS mutated. Until now no specific targeted therapy is available for KRAS mutated NSCLC patients. Optimization of treatment in advanced NSCLC patients with a KRAS mutation could also be achieved by selecting the best available chemotherapy treatment.~Two standard chemotherapy schemes are frequently used and FDA and EMA approved as first line treatment for patients with adenocarcinoma: cisplatin-pemetrexed and carboplatin-paclitaxel-bevacizumab.~The aim of this randomized phase III study is to compare two standard treatment regimens in patients with KRAS mutated, advanced stage NSCLC and the hypothesis is that bevacizumab with chemotherapy improves outcomes compared to chemotherapy alone as first line treatment. Furthermore the outcome for the different KRAS mutations will be studied.~Treatment with one of the two following chemotherapy combinations according to the label: carboplatin-paclitaxel-bevacizumab or cisplatin-pemetrexed q3wks for up to six cycles. Continuation maintenance with bevacizumab and pemetrexed is allowed until progression. Blood and archival tissue will be optionally collected for translational research. This may help to identify subgroups of patients who are likely better treated with a specific treatment regimen.
The purpose of this study is to determine whether carboplatin-paclitaxel-bevacizumab results in a prolonged progression free survival compared to cisplatin-pemetrexed as first line treatment in patients with KRAS mutated non-small cell lung cancer.