In the phase 3 CheckMate 078 study, nivolumab showed significant overall survival (OS) benefit and superior tolerability versus docetaxel in a predominantly Chinese patient population with non-small cell lung cancer (NSCLC). However, data on long-term outcomes with immunotherapy in Asian patients are limited. We report 2-year efficacy and safety data. Patients with advanced/metastatic NSCLC and disease progression after platinum-doublet chemotherapy were randomized 2:1 to nivolumab (3 mg/kg every 2 weeks; n = 338) or docetaxel (75 mg/m2 every 3 weeks; n = 166) until progression, unacceptable toxicity, or other protocol-defined reasons. The primary endpoint was OS; secondary endpoints included progression-free survival, objective response rate, and safety. After 25.9 months minimum follow-up, 21 patients (6 %) remained on nivolumab versus 0 on docetaxel. Median OS was 11.9 months with nivolumab versus 9.5 months with docetaxel (HR: 0.75; 95 % CI: 0.61-0.93); 2-year OS rates were 28 % versus 18 %, respectively. Survival benefits were observed across a variety of predefined subgroups. At 2 years, 39 % and 0 % of responders had ongoing responses with nivolumab and docetaxel, respectively. Grade 3-4 treatment-related adverse events occurred in 12 % of patients with nivolumab versus 47 % with docetaxel, leading to discontinuation in 4 % and 5 % of patients, respectively. No new treatment-related deaths occurred. At 2 years, nivolumab maintained a favorable safety profile and continued to demonstrate superior OS versus docetaxel in this predominantly Chinese patient population with previously treated NSCLC. These data are consistent with long-term outcomes from the global CheckMate 017/057 studies.
Given one-third of the world’s population is infected with Mycobacteriumtuberculosis (MTB), it is important to identify the underling molecular mechanism between development of TB and lung cancer. This study investigated the immune response to MTB infection on lung metastasis in lung cancer cells via T cell-mediated immune response. To clarify this problem, we analyzed the expression levels of PD-1, PD-L1, and PD-L2 and immune function in antigen-specific T cell as derived from MTB patients or spleen lymphocytes derived from wild-type and PD-1 knockout mice with MTB antigen stimulation and Lewis lung cancer cells injection. Our data indicate that the expression levels of PD-1, PD-L1, and PD-L2 were elevated in active pulmonary TB patients, as well as in mice received MTB and lung cancer cells treatment. We also observed the T cell-mediated cellular immune response were inhibited by MTB while MTB significantly promote tumor metastasis in lung. In conclusion, the PD-1/PD-L pathway is required MTB repressed T-cell immune response and promotes tumor metastasis. This study provides evidence that blockade of PD-1/PD-L1 signaling pathway may benefit patients with MTB or other chronic infection and even prevent them from development of cancer.