Anti-PD-L1 therapy yielded durable responses in early NSCLC trials

Dr. Lary Robinson

The PD-L1/PD-1 ligand complex is a natural suppressive pathway used by cells to inhibit IL-2 production and T-cell proliferation so that inflammation is kept under control. However, some remarkably clever cancers including renal cell, ovarian, and non–small cell lung cancer exploit this pathway by up-regulating PD-L1 to evade and hide from the host’s immune system by suppressing inflammation. Four different monoclonal antibodies, such as MPDL3280A, that block PD-L1 have been developed. By blocking this anti-inflammatory pathway, these agents expose the cancer to the host’s activated immune system – the activated "killer" (cytotoxic) T cells.

Early results in a number of phase I clinical trials of anti-PD-L1 agents have shown remarkable and exciting responses using these minimally toxic agents in patients with highly chemoresistant stage IV lung cancer. Somewhat higher responses rates are seen with these agents, and the results are rapid and durable even when treatment is discontinued. This novel immunotherapy approach to systemic treatment of lung cancer is regarded by thoracic oncologists as a potential breakthrough in treatment, and it may soon become the preferred first-line, well-tolerated therapy for this very large group of metastatic lung cancer patients who express high levels of PD-L1, as well as PD-L1–negative tumors. Numerous trials with these agents are ongoing in order to ascertain the most appropriate dosages, potential use with other chemotherapy drugs, and most suitable patient population.

Dr. Lary A. Robinson is professor of thoracic surgery and interdisciplinary oncology at the University of South Florida, Tampa.