ReviewExperimental hematology & oncology2019
The efficacy and safety of combination of PD-1 and CTLA-4 inhibitors: a meta-analysis.
Review in Experimental hematology & oncology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
61 citing papers in PubMed, 2 syntheses or guidelines pooled it, 98 citations in OpenAlex.
- Checkpoint inhibitors as dual immunotherapy in advanced non-small cell lung cancer: a meta-analysis.Frontiers in oncology · 2023Pooled it
- Comparison of Efficacy and Safety of Single and Double Immune Checkpoint Inhibitor-Based First-Line Treatments for Advanced Driver-Gene Wild-Type Non-Small Cell Lung Cancer: A Systematic Review and Network Meta-Analysis.Frontiers in immunology · 2021Pooled it
- A phase Ib study evaluating the safety and efficacy of IBI310 plus sintilimab in patients with advanced non-small-cell lung cancer who have progressed after anti-PD-1/L1 therapy.Cancer medicine · 2024Trial
- Clinical Impact of CTLA4 and LAG3 Single-Nucleotide Polymorphisms in Multiple Myeloma Patients Treated With BCMA CAR T-Cell Therapy.Hematological oncology · 2026Article
- T cell senescence and exhaustion: molecular mechanisms and immune rejuvenation for cancer immunotherapy.Signal transduction and targeted therapy · 2026Review
- Translational insights and clinical challenges of targeting cancer stem cells.Signal transduction and targeted therapy · 2026Review
- Immunotherapy in hepatocellular carcinoma: translating mechanistic insights into clinical advances.Clinical and experimental medicine · 2026Review
- Mild microwave hyperthermia promotes mitotic catastrophe, induces time-delayed cGAS-STING activation and restores sensitivity to anti-PDL1 therapy in Pan02 pancreatic cancer model.Oncoimmunology · 2025Article
- Combining Immune Checkpoint Inhibitors and Anti-Angiogenesis Approaches: Treatment of Advanced Non-Small Cell Lung Cancer.Medical sciences (Basel, Switzerland) · 2025Review
- Microbiome dysbiosis and immune checkpoint inhibitors: Dual targets in Hepatocellular carcinoma management.World journal of hepatology · 2025Review
- Therapeutic Strategies for Drug-resistant Melanoma and Their Clinical Implications.Journal of cancer prevention · 2025Review
- Knockdown of RFC4 inhibits cell proliferation of oral squamous cell carcinoma in vitro and in vivo.FEBS open bio · 2025Article
- CTLA-4 and PD-1 combined blockade therapy for malignant melanoma brain metastases: mechanisms, challenges, and prospects.Frontiers in immunology · 2025Review
- Immune Checkpoints in B Cells: Unlocking New Potentials in Cancer Treatment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Review
- An in situ depot for the sustained release of a TLR7/8 agonist in combination with a TGFβ inhibitor promotes anti-tumor immune responses.Nature communications · 2024Article
- The Immune Checkpoint BTLA in Oral Cancer: Expression Analysis and Its Correlation to Other Immune Modulators.International journal of molecular sciences · 2024Article
- Regulatory mechanisms of PD-1/PD-L1 in cancers.Molecular cancer · 2024Review
- The enhanced antitumor activity of bispecific antibody targeting PD-1/PD-L1 signaling.Cell communication and signaling : CCS · 2024Review
- Investigation of the potential effects of estrogen receptor modulators on immune checkpoint molecules.Scientific reports · 2024Article
- Cell-cell communication network-based interpretable machine learning predicts cancer patient response to immune checkpoint inhibitors.Science advances · 2024Article
1 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundRecently, a series of clinical trials showed that combination of anti-programmed cell death-1 (α-PD-1) and anti-cytotoxic T-lymphocyte-associated protein 4 (α-CTLA-4) could effectively eliminate tumor. However, in comparison with widely adopted mono-immune checkpoint inhibitors, chemotherapy, and targeted therapy, the advantage of combination therapy of α-PD-1 and α-CTLA-4 in response rate and prognosis is controversial especially considering probably increased treatment related adverse event. Thus, we conducted this meta-analysis to explore the efficacy and safety of combination treatment of α-PD-1 and α-CTLA-4.
methodsThis meta-analysis involved 8 clinical trials. In most trials, the primary endpoint was objective response rate (ORR). Thus we calculated risk ratio (RR) and 95% confidence interval (CI) to compare ORR of patients undergoing different treatment strategies. Moreover, the co-primary endpoints in few trials included progression-free survival and overall survival. Hazard ratio (HR) with 95% CI were employed to weigh the influence of different treatments on prognosis of patients. Subgroup analysis was conducted in patients with high and low expression of PD-L1. Lastly, the safety of combination therapy was evaluated by comparing treatment related adverse events among various treatment groups.
resultsOur results showed that ORR was significantly higher in patients receiving α-PD-1 plus α-CTLA-4 compared with α-PD-1 (RR 1.31, 95% CI 1.16-1.48) or α-CTLA-4 monotherapy (RR 2.11, 95% CI 1.84-2.43), chemotherapy and targeted therapy (RR 1.41, 95% CI 1.26-1.58). α-PD-1 plus α-CTLA-4 treated patients had a great advantage on monotherapy, chemotherapy and targeted therapy treated patients in PFS. Notably, no significant alteration in total adverse event rate was observed in α-PD-1 plus α-CTLA-4 treated patients. Results of subgroup analysis showed that combination therapy could enhance anti-tumor response in comparison with other treatments, especially for low PD-L1 expression patients undergoing nivolumab treatment (ORR: RR 1.35, 95% CI 1.11-1.65).
conclusionCombination treatment of α-PD-1 and α-CTLA-4 is a feasible strategy with enhanced efficacy and acceptable adverse event. Moreover, for some low PD-L1 expression patients, α-CTLA-4 might decrease the risk of resistance to α-PD-1 and demonstrate the synergistic anti-tumor effect.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.