Yuanchao Shi1, Jingwei Duan1, Quanlin Guan2, Penglong Xue3, Ya Zheng4. 1. The Lanzhou University, The First Clinical Academy of Lanzhou University, Lanzhou 730000, Gansu, China. 2. Department of Surgical Oncology, The Lanzhou University First Hospital, Lanzhou 730000, Gansu, China. Electronic address: guanquanlin@163.com. 3. Department of Oncology, The Xi an Ninth Hospital, Xi an 710000, Shanxi, China. 4. Department of Gastroenterology, The Lanzhou University First Hospital, Lanzhou 730000, Gansu, China.
Abstract
BACKGROUND: Effective improvement for the programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors had been shown in advanced non-small cell lung cancer (NSCLC) patients compared with traditional therapy. However, we do not have ample evidences to demonstrate the safety and effectivity in the treatment of PD-L1-positive, advanced NSCLC. The relation was controversial about the expression of PD-L1 and survival outcomes of PD-1/PD-L1 inhibitors. MATERIALS AND METHODS: Electronic databases (PubMed, EMBASE, and the Cochrane library) and major conference proceedings were systematically searched for all clinical trials in NSCLC using PD-1/PD-L1 inhibitors. Randomized controlled trials (RCTs) were included to compare PD-1/PD-L1 inhibitors with chemotherapy in advanced NSCLC patients reporting adverse events (AEs) and immune-related AEs (irAEs). The incidence, Hazard Ratio (HR), Odds Ratio (OR), and corresponding 95% confidence interval (CI) of outcomes were calculated. RESULTS: A total of 4939 patients from 10RCTs were included. In the group of PD-L1 ≥ 1%, PD-L1 ≥ 5%, PD-L1 ≥ 10%, PD-L1 ≥ 50%, the HR of OS is 0.31(95%CI 0.38-0.23; p < 0.0001), 0.47(95%CI 0.82-0.12; p = 0.008), 0.85(95%CI 1.17-0.53; p < 0.0001), 0.47(95%CI 0.59-0.36; p < 0.0001) respectively. The HR of PFS is 0.13(95%CI 0.01-0.24; p = 0.027), 0.31(95%CI 0.00-0.62; p < 0.0001), 0.62(95%CI 0.30-0.93; p < 0.0001), 0.40(95% CI 0.20-0.59; p < 0.0001) respectively. In terms of summary adverse events, PD-1/PD-L1 inhibitors groups had a significant lower risks in any treat-realated AEs than chemotherapy. About irAEs, PD-1/PD-L1 inhibitors groups had a significant higher risks in irAEs than chemotherapy. CONCLUSION: PD-1/PD-L1 inhibitors are generally effected and safer than chemotherapy for patients with PD-L1-positive, advanced NSCLC. However, PD-1/PD-L1 inhibitors can generate a unique spectrum of irAEs, and even life-threatening.
BACKGROUND: Effective improvement for the programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors had been shown in advanced non-small cell lung cancer (NSCLC) patients compared with traditional therapy. However, we do not have ample evidences to demonstrate the safety and effectivity in the treatment of PD-L1-positive, advanced NSCLC. The relation was controversial about the expression of PD-L1 and survival outcomes of PD-1/PD-L1 inhibitors. MATERIALS AND METHODS: Electronic databases (PubMed, EMBASE, and the Cochrane library) and major conference proceedings were systematically searched for all clinical trials in NSCLC using PD-1/PD-L1 inhibitors. Randomized controlled trials (RCTs) were included to compare PD-1/PD-L1 inhibitors with chemotherapy in advanced NSCLCpatients reporting adverse events (AEs) and immune-related AEs (irAEs). The incidence, Hazard Ratio (HR), Odds Ratio (OR), and corresponding 95% confidence interval (CI) of outcomes were calculated. RESULTS: A total of 4939 patients from 10RCTs were included. In the group of PD-L1 ≥ 1%, PD-L1 ≥ 5%, PD-L1 ≥ 10%, PD-L1 ≥ 50%, the HR of OS is 0.31(95%CI 0.38-0.23; p < 0.0001), 0.47(95%CI 0.82-0.12; p = 0.008), 0.85(95%CI 1.17-0.53; p < 0.0001), 0.47(95%CI 0.59-0.36; p < 0.0001) respectively. The HR of PFS is 0.13(95%CI 0.01-0.24; p = 0.027), 0.31(95%CI 0.00-0.62; p < 0.0001), 0.62(95%CI 0.30-0.93; p < 0.0001), 0.40(95% CI 0.20-0.59; p < 0.0001) respectively. In terms of summary adverse events, PD-1/PD-L1 inhibitors groups had a significant lower risks in any treat-realated AEs than chemotherapy. About irAEs, PD-1/PD-L1 inhibitors groups had a significant higher risks in irAEs than chemotherapy. CONCLUSION:PD-1/PD-L1 inhibitors are generally effected and safer than chemotherapy for patients with PD-L1-positive, advanced NSCLC. However, PD-1/PD-L1 inhibitors can generate a unique spectrum of irAEs, and even life-threatening.