Targeting the PD-1/PD-L1 Axis in Non-Small-Cell Lung Cancer

Publication date: Available online 23 December 2016
Source:Current Problems in Cancer
Author(s): Rajiv Kumar, Dearbhaile Collins, Saoirse Dolly, Fiona McDonald, Mary E.R. O′Brien, Timothy A. Yap
The last decade has witnessed rapid advances in the discovery and development of immune checkpoint inhibitors in cancer medicine, particularly drugs targeting programmed cell death 1 and programmed cell death ligand-1 in non-small cell lung cancer. The proven antitumor efficacy coupled with low rates of drug-related toxicities observed, albeit idiosyncratic, with these novel immunotherapeutics, have led to the registration of multiple programmed cell death 1 and programmed cell death ligand-1 inhibitors, such as nivolumab, pembrolizumab and atezolizumab, in second-line advanced non-small cell lung cancer, while durvalumab and avelumab are in late phase clinical testing. Moreover, pembrolizumab has shown a survival advantage in the first-line setting, however nivolumab failed to show a survival benefit possibly relating to patient selection on the basis of PD-L1 expression. Current patient selection is based on PD-L1 expression, using the relevant companion diagnostic test, where patients with strong PD-L1 expression being more likely to respond to these novel agents. Ongoing clinical research is now focused on the development of programmed cell death 1 and programmed cell death ligand-1 inhibitor monotherapy in neo-adjuvant and adjuvant non-small cell lung cancer. There is also much interest in using these drugs as a therapeutic backbone for rational combinations with other treatment modalities, including cytotoxic chemotherapies in the first line non-small cell lung cancer, other immunotherapies such as cytotoxic T-lymphocyte-associated protein-4 antagonists, molecularly targeted agents, including EGFR and ALK inhibitors, and radiotherapy. Concurrent treatment with radiotherapy is of particular interest due to the potential for the abscopal effect, whereby using radiotherapy to facilitate systemic treatment.



http://ift.tt/2ibC0Z7