[Stage IV NSCLC. Biological treatments of lung cancer in 2008... and in the near future].

Nowadays, biological cancer treatments represent the major advance in non-small cell lung cancer therapeutic strategies. During the last decade, more than 15 randomized trials associating chemo with biological treatments, in first line setting, have included more than 12,073 NSCLC patients, and as much in phase 2-3 trials in second and third line setting. Very few were positive, but currently anti-angiogenic strategy using the humanized monoclonal antibody bevacizumab has been approved in association with chemotherapy, in first line treatment of carefully selected NSCLC patients (with non proximal tumors, without cerebral metastasis, and of non-squamous histology). On the same way, monotherapy by the EGFR tyrosine kinase inhibitor erlotinib has been approved in second and third line setting, with comparable results as chemotherapy. 2008 was the year of new targeted therapies with cetuximab, the chimeric monoclonal antibody directed against EFGR, in association with chemotherapy in first line setting, whereas EGFR TKI are also tested in first line, in patients selected on the ground of the molecular properties of their tumors (with EGFR mutation or positive EGFR FISH). New generation EGFR TKI (more potent if not more selective) are developed in new settings (neo-adjuvant or adjuvant treatment), with promising results in phase 2 trials, whereas active immunotherapy directed toward MUC1 or MAGE-A3 are tested in large phase 3 randomized trials in adjuvant setting (post-surgery or post-radiotherapy), since phase 2 results were appealing. Therefore, during the last few years, targeted therapies quit science-fiction to enter in our current practice, leading clinicians to learn how to treat new kinds of toxicities and to select patients on molecular grounds.