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Anti-PD-1 and Anti-PD-L1 in Head and Neck Cancer: A Network Meta-Analysis
Andrea Botticelli1, Alessio Cirillo2, Lidia Strigari3
1Department of Clinical and Molecular Oncology, "Sapienza" University of Rome, Rome, Italy.
Objective:
The monoclonal antibodies anti-programmed death protein-1 (anti-PD-1) nivolumab and pembrolizumab are the first immune checkpoint inhibitors (ICIs) approved for treatment of recurrent/metastatic head and neck carcinoma R/M HNSCC in first line and in platinum refractory disease. This network meta-analysis aims to investigate the efficacy of anti-PD-1- vs anti-PD-L1-based therapy in R/M HNSCC cancer patients through a systematic review of the literature to provide support for evidence-based treatment decisions. In particular, the effectiveness of ICIs for R/M HNSCC is analyzed according to the different mechanisms of action of the check-points inhibitory drugs in different subgroups of patients.
Methods:
We did a systematic literature review and network meta-analysis (NMA) of randomized controlled trials (RCTs) in PubMed, ClinicalTrials.gov, Embase, Medline, the Cochrane Central Register of Controlled Trials, Web of Science. Our search identified a total of five randomized controlled trials: Keynote 040, Keynote 048, Eagle, Condor, Checkmate 141. These trials included 3001 patients. Treatment was sub-categorized into PD-L1-based, PD-1-based, and standard chemotherapy. Treatments were indirectly compared with anti-PD-L1-based therapy.
Results:
The network meta-analysis demonstrated no significant differences in OS between different subgroups except for the metastatic patients in which anti-PD-1-based therapy was associated with significantly less risk of death. Furthermore, anti-PD-1-based therapy appeared to be effective in smoker patients and in human papilloma-negative (HPV) patients. Conversely, anti-PD-L1-based therapy seems to be better efficient in female patients, in locally recurrent setting and in HPV positive patients.
Conclusion:
This is the first NMA study that aimed to indirectly compare anti-PD-1- and anti-PD-L1-based therapy in HNSCC patients. The results of our NMA could help define a profile of patient responder or resistant to specific classes of immune drugs and can be used to guide/design future studies in the novel scenario of precision immune-oncology.
Insights
This network meta-analysis compared anti-PD-1 and anti-PD-L1 therapies for recurrent/metastatic head and neck cancer. Anti-PD-1 therapy showed better survival in metastatic patients, smokers, and HPV-negative individuals.
Area of Science:
- Oncology
- Immunotherapy
- Clinical Trials
Background:
- Recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) has limited treatment options.
- Immune checkpoint inhibitors (ICIs), including anti-programmed death protein-1 (anti-PD-1) and anti-programmed death-ligand 1 (anti-PD-L1) therapies, are approved for R/M HNSCC.
- Evidence comparing the efficacy of anti-PD-1 versus anti-PD-L1 based therapies is needed to guide clinical decision-making.
Purpose of the Study:
- To conduct a network meta-analysis (NMA) comparing the efficacy of anti-PD-1-based versus anti-PD-L1-based therapies in patients with R/M HNSCC.
- To analyze ICI effectiveness in different patient subgroups based on ICI mechanism of action.
Main Methods:
- Systematic literature review and NMA of randomized controlled trials (RCTs).
- Searched databases including PubMed, Embase, Medline, and Cochrane.
- Included five RCTs with 3001 patients, categorizing treatments into PD-L1-based, PD-1-based, and standard chemotherapy.
Main Results:
- No significant overall survival differences were found between subgroups, except for metastatic patients where anti-PD-1 therapy showed a reduced risk of death.
- Anti-PD-1 therapy was more effective in smokers and human papilloma virus-negative (HPV-) patients.
- Anti-PD-L1 therapy demonstrated greater efficacy in female patients, locally recurrent settings, and HPV-positive patients.
Conclusions:
- This is the first NMA to indirectly compare anti-PD-1 and anti-PD-L1 therapies in HNSCC.
- Results may help define patient profiles responsive to specific ICIs.
- Findings can inform future precision immuno-oncology studies and treatment strategies.
