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Published on: February 5, 2020
Network Meta-analysis Comparing Efficacy, Safety and Tolerability of Anti-PD-1/PD-L1 Antibodies in Solid Cancers
Laith Al-Showbaki1, Michelle B Nadler1, Alexandra Desnoyers1
1Department of Medical Oncology and Hematology, Princess Margaret Cancer Center, University Health Network, Faculty of Medicine, University of Toronto, Toronto, Canada.
Abstract:
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.
Insights
Comparing immune checkpoint inhibitors, pembrolizumab, nivolumab, and atezolizumab show similar efficacy. Avelumab appears less effective, while avelumab offers better safety, unlike atezolizumab and pembrolizumab.
Area of Science:
- Oncology
- Immunotherapy
- Pharmacology
Background:
- Multiple anti-programmed cell death protein 1 (PD-1)/PD-1 ligand (PD-L1) antibodies are approved.
- Comparative efficacy, safety, and tolerability data are lacking for these agents.
Purpose of the Study:
- To conduct a network meta-analysis comparing the efficacy, safety, and tolerability of single-agent anti-PD-1/PD-L1 inhibitors.
- To inform clinical decision-making when multiple immunotherapy options are available.
Main Methods:
- Systematic review of randomized controlled trials (RCTs) supporting registration of anti-PD-1/PD-L1 inhibitors (2015-2019).
- Network meta-analysis extracting hazard ratios (HR) for overall survival and odds ratios (OR) for safety outcomes.
- Pair-wise comparisons between different anti-PD-1/PD-L1 antibodies.
Main Results:
- Sixteen RCTs with 10,673 patients were analyzed across various cancers.
- Pembrolizumab, nivolumab, and atezolizumab demonstrated similar efficacy; avelumab showed inferior efficacy.
- Avelumab exhibited better safety and tolerability, while atezolizumab and pembrolizumab were associated with more adverse events.
Conclusions:
- Pembrolizumab, nivolumab, and atezolizumab are comparable in efficacy for approved indications.
- Avelumab demonstrates lower efficacy but potentially improved safety.
- Atezolizumab and pembrolizumab show higher rates of adverse events compared to avelumab.
