Immunotherapy and new frontiers in the treatment of lung cancer

Lung cancer is the malignancy with a high mortality rate. Despite considerable progresses in targeted therapy, advanced lung cancer patients have not experienced a substantial improvement of survival. In the last few years, immune checkpoint inhibitors (ICIs) have represented as promising therapeutic agents in non-small cell lung cancer (NSCLC). In numerous randomized studies, PD-1/PD-L1 inhibitors have allowed to obtain significant improvements in overall survival (OS) with response rates much higher and more durable than single-agent docetaxel in patients with pretreated, advanced NSCLC. Therefore, PD-1 inhibitors such as nivolumab and pembrolizumab were rapidly approved by the United States Food and Drug Administration (FDA) for both squamous and non-squamous lung cancer in the second-line setting. These encouraging results have led to change the current therapeutic paradigm of metastatic NSCLC also for first-line treatment, adding a new standard option for patients with PD-L1-positive tumors. Pembrolizumab, was approved by FDA in October 2016 for treatment-naïve advanced NSCLC patients with tumor high PD-L1 expression and tumor proportion score (TPS) ≥50%. Combining immunotherapy with novel immunomodulatory agents, chemotherapy or radiation therapy are currently being evaluated to achieving higher response rates and improving OS rate. The correct combination and order of therapy is under investigation. In this review, we discuss the clinical results and safety data for the treatment-naïve and pretreated settings in both early and advanced NSCLC. An update of the future perspectives will also be discussed.