Comparative Efficacy and Safety of PD-1/PD-L1 Inhibitors for Patients with Solid Tumors: A Systematic Review and Bayesian Network Meta-analysis

Qingyuan Huang; Yuzhen Zheng; Zhendong Gao; Lianxiong Yuan; Yihua Sun; Haiquan Chen

doi:10.7150/jca.49325

Comparative Efficacy and Safety of PD-1/PD-L1 Inhibitors for Patients with Solid Tumors: A Systematic Review and Bayesian Network Meta-analysis

J Cancer. 2021 Jan 1;12(4):1133-1143. doi: 10.7150/jca.49325. eCollection 2021.

Authors

Qingyuan Huang^{1

2

3}, Yuzhen Zheng^{4

5}, Zhendong Gao^{1

2

3}, Lianxiong Yuan⁶, Yihua Sun^{1

2

3}, Haiquan Chen^{1

2

3}

Affiliations

¹ Department of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer Center, Shanghai, China.
² Institute of Thoracic Oncology, Fudan University, Shanghai, China.
³ Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
⁴ Department of Thoracic Surgery, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China.
⁵ Department of Thoracic Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
⁶ Office of Research Service, Third Affiliation Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China.

Abstract

Purpose: The clinical use of immunotherapies targeting programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) is rapid expanding, but the equivalency of these inhibitors remains unclear. We aimed to comprehensively compare the efficacy and safety of PD-1/PD-L1 inhibitors with a systematic review and Bayesian network meta-analysis Methods: We searched PubMed, Web of Knowledge, related reviews and abstracts for randomized controlled trials of five PD-1/PD-L1 inhibitors for patients with solid tumors before November 30^th, 2018. We estimated summary hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), and odds ratios (ORs) for grade 3-5 treatment-related adverse events (TrAEs) using pairwise and network meta-analysis with random-effects. This study was registered with PROSPERO (#CRD42018116624). Results: Totally, 43 reports of 35 trials comprising 21261 patients were eligible for the analysis. Nivolumab, pembrolizumab, atezolizumab and durvalumab were more effective than control treatment, and no significant differences were identified in OS and PFS between any two inhibitors. Avelumab was associated with significantly inferior OS to nivolumab (HR 1.37, 95%CrI 1.05-1.78) and pembrolizumab (HR 1.33, 95%CrI 1.02-1.73), and with inferior PFS to nivolumab (HR 1.60, 95%CrI 1.03-2.51). Compared with placebo, nivolumab had increased risk of grade 3-5 TrAEs (OR 2.35, 95%CrI 1.35-4.17). Compared with standard-of-care, nivolumab (OR 0.39, 95%CrI 0.28-0.54), pembrolizumab (OR 0.43, 95%CrI 0.30-0.60), atezolizumab (OR 0.37, 95%CrI 0.21-0.64) and avelumab (OR 0.24, 95%CrI 0.12-0.48) significantly reduced grade 3-5 TrAEs. There were not significant differences in grade 3-5 TrAEs between any two inhibitors. Conclusion: This Bayesian network meta-analysis revealed that nivolumab, pembrolizumab, atezolizumab and durvalumab yielded equivalent survival, while avelumab was associated with unfavorable survival. PD-1/PD-L1 inhibitors were comparable in the risk of TrAEs, and safer than conventional therapies.