Hepatotoxicity in patients with solid tumors treated with PD-1/PD-L1 inhibitors alone, PD-1/PD-L1 inhibitors plus chemot
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REVIEW
Hepatotoxicity in patients with solid tumors treated with PD-1/PD-L1 inhibitors alone, PD-1/PD-L1 inhibitors plus chemotherapy, or chemotherapy alone: systematic review and meta-analysis Xiaodi Guo 1 & Wendong Li 1 & Jiexuan Hu 2 & Emily C. Zhu 3 & Qiang Su 2 Received: 2 March 2020 / Accepted: 15 May 2020 # The Author(s) 2020
Abstract Background 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. Methods 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. Results 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. Conclusions Relative to chemotherapy alone, PD-1/PD-L1 inhibitors with or without chemotherapy increased the risk of allgrade and high-grade hepatitis, but generally did not increase the risk of elevated blood markers of hepatotoxicity. Keywords Hepatotoxicity . PD-1/PD-L1 inhibitors . Chemotherapy . Meta-analysis . Solid tumors
Introduction
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00228-020-02903-2) contains supplementary material, which is available to authorized users. * Qiang Su [email protected] 1
Department of Oncology, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
2
Department of Oncology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
3
Department of CIS & Quantitative Methods, McCoy College of Business, Texas State University, San Marcos, TX, USA
Cancer has been a leading cause of mortality among people younger than 70 years old for more than 50 years [1]. Although cancer treatments are expensive throughout the world, there are lim
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