Unmet Needs in the Treatment of Metastatic Non-small-cell Lung Cancer

Abstract

Today, lung cancer remains the most common cause of cancer-related mortality in the world. Non-small-cell lung cancer (NSCLC) accounts for approximately 85% of lung cancer, and 40% of these patients present at an advanced stage, including patients with metastatic disease and those with locally advanced disease with malignant pleural or pericardial effusion.1 Platinum-based chemotherapy with third-generation agents (gemcitabine, vinorelbine, docetaxel or paclitaxel) improves survival and quality of life compared with best supportive care alone. Despite these advances in treatment, a therapeutic plateau has been reached using conventional chemotherapy. Over the past decade, large randomised studies have demonstrated the relative equivalence of platinum-based doublets, with response rates of 16‐32% and median survival ranging from eight to 11 months, with one- and two-year survival rates of 35‐45% and 10‐20%, respectively. The majority of patients experience disease progression, generally after a median of three to six months of initiating chemotherapy, and the long-term prognosis is still poor.2 Therefore, there is a great unmet need to provide more effective therapeutic strategies to further improve outcome in patients with advanced NSCLC. Further understanding of cancer biology has allowed the development of several potential molecular targets for cancer treatment. Numerous targeted agents have been evaluated in clinical trials of cancer treatment, and a number of phase III trials have generated definite results. In particular, several agents that target the epidermal growth factor receptor (EGFR) and the angiogenesis pathway have proved efficacious in the management of NSCLC. To further improve the outcome of first-line therapy for advanced NSCLC, there is much interest in adding these targeted agents to platinumbased chemotherapy. This article will focus on the potential beneficial role of these targeted agents in the management of advanced NSCLC in the first-line treatment setting.