J Cancer 2021; 12(14):4372-4378. doi:10.7150/jca.57413

Research Paper

Network Meta-analysis Comparing Efficacy, Safety and Tolerability of Anti-PD-1/PD-L1 Antibodies in Solid Cancers

Laith Al-Showbaki, Michelle B. Nadler, Alexandra Desnoyers, Fahad A. Almugbel, David W. Cescon, Eitan Amir

Department of Medical Oncology and Hematology, Princess Margaret Cancer Center, University Health Network, Faculty of Medicine, University of Toronto, Toronto, Canada.

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Al-Showbaki L, Nadler MB, Desnoyers A, Almugbel FA, Cescon DW, Amir E. Network Meta-analysis Comparing Efficacy, Safety and Tolerability of Anti-PD-1/PD-L1 Antibodies in Solid Cancers. J Cancer 2021; 12(14):4372-4378. doi:10.7150/jca.57413. Available from https://www.jcancer.org/v12p4372.htm

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Background: Multiple anti-PD-1/PD-L1 antibodies have been approved, and in some diseases, there is a choice of more than one. Comparative efficacy, safety and tolerability are unknown.

Methods: Randomized trials (RCTs) supporting the registration of single agent anti-PD1 or anti-PDL1 inhibitors between 2015-2019 were identified. We extracted the hazard ratio (HR) for overall survival (OS) and calculated the odds ratio (OR) for commonly reported safety and tolerability outcomes. We then performed a network meta-analysis, reporting multiple pair-wise comparisons between different anti-PD-1/PD-L1 antibodies.

Results: Sixteen RCTs comprising 10673 patients were included; 10 in non-small-cell lung cancer, 2 in melanoma, 2 in head and neck squamous cell carcinoma and 2 in urothelial cancer. Compared to pembrolizumab, efficacy was similar for nivolumab (HR: 1.02 95% CI: 0.91-1.14) and for atezolizumab (HR: 0.97 95% CI: 0.85-1.10), however, avelumab appeared inferior (HR: 1.30, 95% CI: 1.06-1.56). Pembrolizumab showed similar odds of serious adverse events (SAEs) as nivolumab (OR: 1.12, 95% CI: 0.56-2.27) and atezolizumab (OR: 1.05, 95% CI: 0.55-2.04). Compared to nivolumab, atezolizumab was associated with more SAEs (OR: 2.14, 95% CI: 1.47-3.12). Avelumab had the lowest odds of grade 3-4 adverse events compared to pembrolizumab (OR: 0.42, 95% CI: 0.24-0.74), nivolumab (OR: 0.38, 95% CI: 0.24-0.62) and atezolizumab (OR: 0.21, 95% CI: 0.14-0.33). The odds of treatment discontinuation without progression were similar between nivolumab and atezolizumab (OR: 1.20, 95% CI: 0.73-2.00), and between pembrolizumab and nivolumab (OR: 1.35, 95% CI: 0.83-2.17), but was higher with atezolizumab compared to nivolumab (OR: 2.56, 95% CI: 1.29-5.00). Pembrolizumab was associated with higher OR of immune-related adverse events (IRAEs) compared to nivolumab (OR: 2.12, 95% CI: 1.49-3.03) and atezolizumab (OR: 1.63, 95% CI: 1.09-2.43).

Conclusions: Pembrolizumab, nivolumab, and atezolizumab have similar efficacy. Avelumab appears less efficacious. Safety and tolerability seem better with avelumab, but worse with atezolizumab and pembrolizumab.

Keywords: Immunotherapy, Programmed Cell Death 1 Receptor, Review, Clinical Trial, Phase III as Topic