Targeting PD-I/PD-LI in lung cancer: Current perspectives

Abstract

Increased understanding of tumor immunology has led to the development of effective immunotherapy treatments. One of the most important advances in this field has been due to pharmacological design of antibodies against immune checkpoint inhibitors. Anti-PD-1/ PD-L1 antibodies are currently in advanced phases of clinical development for several tumors, including lung cancer. Results from Phase I-III trials with anti-PD-1/PD-L1 antibodies in nonsmall-cell lung cancer have demonstrated response rates of around 20% (range, 16%–50%). More importantly, responses are long-lasting (median duration of response, 18 months) and fast (50% of responses are detected at time of first tumor evaluation) with very low grade 3–4 toxicity (less than 5%). Recently, the anti-PD-1 antibody pembrolizumab received US Food and Drug Administration (FDA) breakthrough therapy designation for treatment of non-small-cell lung cancer, supported by data from a Phase Ib trial. Another anti-PD-1 antibody, nivolumab, has also been approved for lung cancer based on survival advantage demonstrated in recently released data from a Phase III trial in squamous cell lung cancer.