Research on immune target inhibitors in lung cancer is widespread, especially PD-1 (programmed cell death-1) and PD-L1 (programmed death ligand 1) inhibitors. These agents, alone or in combination, appear to have the potential to change the current clinical treatment of NSCLC. The use of immunotherapy in non-small cell lung cancer is making a massive comeback, and new data show it has a very promising future in the treatment of lung cancer. The need for such therapy in non-small cell lung cancer is more urgent than ever, with cytotoxic systemic chemotherapy remaining the backbone of treatment. said Chandra P. Belani, MD, PhD, of the Hershey Cancer Institute in Pennsylvania. At the 2014 Chemotherapy Fundamentals Symposium, Dr. Belani spoke to an audience about advances in immunotherapy research. PD-1 and PD-L1 proteins are immune target inhibitors, and immunotherapy that acts directly on these targets can release braking signals to the immune system to attack tumor cells. Anti-PD-1 and anti-CPD-L1 inhibitors have shown efficacy in a variety of tumor types, including lung cancer. The anti-PD-1 inhibitor Nivolumab, an anti-PD-1 inhibitor, has been shown to achieve an overall remission rate of 17% and a duration of remission of at least 18 months in patients with non-small cell lung cancer who have been treated with multiple prior therapies. All three doses showed a median overall survival of 9.2 months for patients with squamous cell carcinoma and 10.1 months for patients with non-squamous cell carcinoma. 3 mg/kg resulted in a median overall survival of 18.2 months for patients with non-squamous cell carcinoma, which will be further investigated in a phase III trial. Pembrolizumab (Keytruda) also showed high activity in patients with previously treated non-small cell lung cancer treated with multiple modalities, with overall remission rates of 21%, 19%-23% in PD-L1-positive non-small cell lung cancer patients, and 9%-13% in PD-L1-negative non-small cell lung cancer patients. Data on median duration of remission were not available at the time of this analysis. In early studies in non-small cell lung cancer, nivolumab and pembrolizumab showed high activity in patients with non-small cell lung cancer who had been previously treated with multiple approaches and in all patients. There is evidence that PD-L1-expressing tumors are more sensitive to these drugs, but remissions have also been seen in PD-L1-negative patients, Dr. Belani explained. However, pembrolizumab was developed for PD-L1-positive patients. He said. The FDA granted pembrolizumab breakthrough designation based on the drug’s efficacy in EGFR-negative, ALK-negative patients and in patients whose disease progressed on or after platinum-based chemotherapy. Dr. Belani noted that pembrolizumab is the first immunotherapy drug approved for use in non-small cell lung cancer. Anti-PD-L1 inhibitors He went on to say that the premier PD-L1 antibody currently under investigation is MPDL3280A, which was developed for PD-L1-positive patients and announced at the 2013 World Lung Cancer Conference that it achieved an overall remission rate of 23% in all patients with non-small cell lung cancer. [4] The remission rate was even higher in patients who were former or current smokers. “But don’t tell your patients to smoke”, he said. A phase I trial of the anti-CPD-L1 inhibitor MEDI4736 showed remission rates of 39% and 5% for PD-L1-positive and negative patients, respectively. So the question is, do these immunotherapies work only for PD-L1-positive non-small cell lung cancer or also for PD-L1-negative non-small cell lung cancer? He noted that in all the studies, both anti-PD-L1 drugs had higher remission rates in PD-L1-positive patients. On the other hand, he noted, there was no significant correlation between PD-L1 expression and remission rates and survival in the studies on nivolumab. There is also the problem that there are conflicting assays for PD-L1, and PD-L1 expression is not currently a definitive biomarker. Many studies applying anti-PD-1 or anti-PD-L1 inhibitors to non-small cell lung cancer are currently underway (3 trials), one of which is studying the efficacy of nivolumab in 3 or more lines of treatment for squamous cell non-small cell lung cancer, and the other 2 trials are studying its efficacy in first-line treatment. MEDI4736 has been used in the large, biomarker-driven Lung-MAP trial in advanced squamous cell carcinoma, and one of the five treatment arms will compare the efficacy of the drug with docetaxel chemotherapy. We do not know the EGFR or ALK mutation status of the patients participating in this trial.