Novel drugs against non-small-cell lung cancer.

Objective: Important therapeutic advances for patients with advanced non-small-cell lung cancer (NSCLC) with focus on individualized therapy have recently occurred and are summarized in this review.

Results: Cetuximab added to first-line chemotherapy has been shown to improve survival in patients with high epidermal growth factor receptor (EGFR) expression in their tumors. Afatinib has shown improved progression-free survival and better quality of life compared to chemotherapy in patients with EGFR-mutation-positive adenocarcinomas. Several other EGFR-directed agents are in clinical development. Crizotinib improved progression-free survival compared to second-line chemotherapy with docetaxel or pemetrexed in patients with advanced anaplastic lymphoma kinase-positive NSCLC. Selumetinib added to docetaxel has improved outcome compared with docetaxel in a randomized phase II trial in patients with advanced KRAS-mutant NSCLC and this combination is currently studied in a phase III trial. Nintedanib added to docetaxel improved progression-free survival in the second-line therapy of patients with advanced NSCLC but many other angiogenesis inhibitors failed to improve clinical outcome in phase III trials. Several other targeted therapies are currently evaluated in phase III trials in patients with advanced NSCLC.

Conclusions: Recent trials have led to the approval of afatinib and crizotinib for subsets of patients with advanced NSCLC.