Treatment of non-small-cell lung cancer: state of the art and development of new biologic agents

Conventional treatment of non-small-cell lung cancer (NSCLC) has apparently reached a plateau of effectiveness in improving the survival of NSCLC patients. Although neoadjuvant and adjuvant therapies in early stages are under investigation and some progress has been achieved in the management of locally advanced and advanced disease, treatment outcomes for NSCLC are still to be considered dismal. The majority of patients affected from NSCLC experience metastatic disease and optimization of chemotherapy is unlikely to produce further substantial survival improvement, with symptom relief and quality of life still being the primary goal of treatment. Based on this background, clinical investigation of novel treatment strategies is mandatory. As our understanding of tumor cell biology has increased and several molecular targets for NSCLC have been identified, a number of new biologic agents have been developed. Targeted therapy describes treatment strategies that focus on cell signaling and other biologic pathways involved in tumorigenesis. Several targeted agents have been introduced in clinical trials in NSCLC, the majority in advanced disease, and some phase III studies have already produced definitive results. Currently, the minority of these new agents offer promise of improved outcomes and negative results are more common to be reported than positive ones. However, important lessons can be learned from this first generation of clinical trials that should be considered the first step of clinical research in this field.