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Published on: September 25, 2018
Comparative Efficacy and Safety of Anti-PD-1/PD-L1 for the Treatment of Non-Small Cell Lung Cancer: A Network
Maofen Jiang1, Chunjiao Liu1, Dongxiao Ding2
1Department of Pathology, Beilun District People's Hospital, Ningbo, China.
Objective:
The present network meta-analysis (NMA) was conducted to summarize the direct and indirect evidence of common programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors including avelumab, atezolizumab, cemiplimab, nivolumab, and pembrolizumab for the treatment of non-small cell lung cancer (NSCLC) patients and further to determine the optimal therapeutic regimen.
Methods:
We performed a systematic literature search to identify all potentially eligible studies in PubMed, Embase, and the Cochrane Library until August 7, 2021. The primary outcome was overall survival (OS), and the second outcome was treatment-related adverse events (TRAEs). We used random-effects model to conduct direct and network meta-analyses, which were performed by using RevMan 5.3 and R version 3.6.1, respectively.
Results:
Direct meta-analysis suggested that atezolizumab, cemiplimab, nivolumab, or pembrolizumab significantly improved OS compared with chemotherapy (CT), and NMA further established that atezolizumab [hazard ratio (HR), 0.77; 95% CrI, 0.62-0.96], nivolumab (HR, 0.75; 95% CrI, 0.62-0.93), or pembrolizumab (HR, 0.71; 95% Credible interval (Crl), 0.57-0.89) significantly and cemiplimab (HR, 0.68; 95% CrI, 0.46-1.02) numerically improved OS compared with CT. Meanwhile, NMA also indicated that cemiplimab was numerically superior to other PD-1/PD-L1 agents. Moreover, avelumab, atezolizumab, cemiplimab, nivolumab, and pembrolizumab were found to have fewer TRAEs compared with CT in direct meta-analysis, which were supported by the results from the NMA. Meanwhile, surface under the cumulative ranking curve (SUCRA) and ranking probability suggested that cemiplimab provided the most favorable balance between efficacy and safety, with the first ranking for the OS.
Conclusions:
Based on available evidence, cemiplimab may have the most favorable risk-benefit ratio for NSCLC patients compared with other common therapeutic management. However, future research with a large-scale, high-quality, and mature follow-up is needed to further determine which agents should be preferentially selected for NSCLC patients due to the limitations of our NMA and variations of eligible studies in treatment line and PD-L1 status.
Insights
Cemiplimab shows a favorable risk-benefit profile for non-small cell lung cancer (NSCLC) patients, demonstrating improved overall survival and fewer treatment-related adverse events compared to chemotherapy. Further research is needed to confirm optimal agent selection.
Area of Science:
- Immunotherapy
- Oncology
- Clinical Trials
Background:
- Non-small cell lung cancer (NSCLC) treatment landscape.
- Role of programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors.
- Need for comparative efficacy and safety data.
Approach:
- Network meta-analysis (NMA) of direct and indirect evidence.
- Systematic literature search up to August 2021.
- Primary outcome: overall survival (OS); Secondary outcome: treatment-related adverse events (TRAEs).
Key Points:
- Atezolizumab, cemiplimab, nivolumab, and pembrolizumab improved OS versus chemotherapy.
- Cemiplimab demonstrated numerical superiority among PD-1/PD-L1 inhibitors for OS.
- All evaluated PD-1/PD-L1 inhibitors showed fewer TRAEs compared to chemotherapy.
Conclusions:
- Cemiplimab may offer the most favorable risk-benefit ratio for NSCLC patients.
- Limitations include study variations and need for large-scale, high-quality future research.
- Optimal agent selection requires further investigation.
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