Recent Clinical Trials in Non-Small Cell Lung Cancer

Non-small cell lung cancer (NSCLC) remains the most common cause of cancer-related mortality worldwide. Considerable progress has been made in recent times that have led to improved outcome for patients with all stages of NSCLC. There is increasing evidence that systemic therapy is integral for the treatment of all stages of NSCLC. Adjuvant chemotherapy has been proven in multiple recent trials to improve survival for patients with surgically resected early stage NSCLC. A combined modality approach consisting of external beam radiation and systemic chemotherapy is regarded as the standard of care for patients with locally advanced, unresectable NSCLC (LA-NSCLC), where it has curative potential. However, for patients with advanced stage or metastatic disease, treatment continues to be palliative, though benefits in survival and quality of life have been established with systemic therapy. While platinum combinations continue to be central to therapy of NSCLC, non-platinum two-drug regimens utilizing novel agents such as the taxanes, gemcitabine, pemetrexed and irinotecan are also in clinical use. The emergence of molecularly targeted agents has also widened the therapeutic arena for NSCLC. Survival benefit has been noted with erlotinib, an inhibitor of the epidermal growth factor receptor, for patients who progressed following 1 or 2 prior chemotherapy regimens. Another targeted approach that has recently emerged as a front-runner is anti-angiogenic therapy. Bevacizumab, a monoclonal antibody against the vascular endothelial growth factor (VEGF), improved survival when combined with chemotherapy for patients with advanced stage non-squamous NSCLC. These exciting developments have contributed to optimism for NSCLC patients and also fuelled enthusiasm among researchers. This article reviews the pivotal clinical trials that have led to important changes in the treatment paradigms for NSCLC in recent years.