Department of Oncology, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China.
Department of Oncology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China.
Eur J Clin Pharmacol. 2020 Oct;76(10):1345-1354. doi: 10.1007/s00228-020-02903-2. Epub 2020 Jun 8.
This meta-analysis examined the risk of hepatotoxicity in patients with solid tumors who received a PD-1/PD-L1 inhibitor alone, a PD-1/PD-L1 inhibitor plus chemotherapy, or chemotherapy alone.
Potentially eligible studies were identified by searches of Embase and PubMed. All included studies were randomized controlled trials (RCTs) that examined patients with solid tumors who received a PD-1/PD-L1 inhibitor and/or chemotherapy.
We included 20 clinical trials (11,634 patients). Thirteen trials compared PD-1/PD-L1 inhibitor monotherapy with chemotherapy. These two groups had similar risk for elevated markers of hepatotoxicity (based on analysis of all marker grades and high marker grades), although the PD-1/PD-L1 inhibitor group had an elevated relative risk (RR) of elevated aspartate aminotransferase (AST; RR = 2.13, 95% CI = 1.04 to 4.36, P = 0.04) when considering high grades alone; however, this disparity was not significant for comparisons of the pembrolizumab and nivolumab subgroups with the chemotherapy group. Compared with chemotherapy, PD-1/PD-L1 inhibitors increased the risk of all-grade hepatitis (RR = 5.85, 95% CI = 1.85 to 18.46, P < 0.01), and high-grade hepatitis (RR = 5.66, 95% CI = 1.58 to 20.27, P < 0.01). Seven other studies compared PD-1/PD-L1 inhibitor plus chemotherapy with chemotherapy alone. The combined treatment led to a higher risk for all-grade hepatitis (RR = 2.14, 95% CI = 1.29 to 3.55, P < 0.01) and high-grade hepatitis (RR = 5.24, 95%CI = 1.89 to 14.52, P < 0.01), but these groups had similar risk for all-grade and high-grade elevated markers of hepatotoxicity.
Relative to chemotherapy alone, PD-1/PD-L1 inhibitors with or without chemotherapy increased the risk of all-grade and high-grade hepatitis, but generally did not increase the risk of elevated blood markers of hepatotoxicity.
本荟萃分析研究了单独使用 PD-1/PD-L1 抑制剂、PD-1/PD-L1 抑制剂联合化疗或单独化疗的实体瘤患者发生肝毒性的风险。
通过对 Embase 和 PubMed 的检索，确定了潜在的合格研究。所有纳入的研究均为检查接受 PD-1/PD-L1 抑制剂和/或化疗的实体瘤患者的随机对照试验 (RCT)。
我们纳入了 20 项临床试验 (11634 例患者)。13 项试验比较了 PD-1/PD-L1 抑制剂单药治疗与化疗。这两组发生肝毒性标志物升高的风险相似(基于所有标志物等级和高标志物等级的分析)，尽管 PD-1/PD-L1 抑制剂组单独考虑高等级时天门冬氨酸氨基转移酶 (AST)升高的相对风险 (RR)升高 (RR = 2.13，95%CI = 1.04 至 4.36，P = 0.04)；然而，当比较 pembrolizumab 和 nivolumab 亚组与化疗组时，这种差异并不显著。与化疗相比，PD-1/PD-L1 抑制剂增加了所有等级肝炎的风险 (RR = 5.85，95%CI = 1.85 至 18.46，P < 0.01) 和高等级肝炎的风险 (RR = 5.66，95%CI = 1.58 至 20.27，P < 0.01)。另外 7 项研究比较了 PD-1/PD-L1 抑制剂联合化疗与单独化疗。联合治疗导致所有等级肝炎的风险更高 (RR = 2.14，95%CI = 1.29 至 3.55，P < 0.01) 和高等级肝炎的风险更高 (RR = 5.24，95%CI = 1.89 至 14.52，P < 0.01)，但这些组发生所有等级和高等级肝毒性标志物升高的风险相似。
与单独化疗相比，联合或不联合化疗的 PD-1/PD-L1 抑制剂增加了所有等级和高等级肝炎的风险，但通常不会增加肝毒性血液标志物升高的风险。
