SynthesisBMC cancer2019
The safety and tolerability of combined immune checkpoint inhibitors (anti-PD-1/PD-L1 plus anti-CTLA-4): a systematic review and meta-analysis.
Synthesis in BMC cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 6 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
51 citing papers in PubMed, 6 syntheses or guidelines pooled it, 90 citations in OpenAlex.
- Efficacy and safety of anti-PD-1/PD-L1-based dual immunotherapies versus PD-1/PD-L1 inhibitor alone in patients with advanced solid tumor: a systematic review and meta-analysis.Cancer immunology, immunotherapy : CII · 2024Pooled it
- Efficacy and safety of nivolumab plus ipilimumab in gastrointestinal cancers: a systematic review and meta-analysis.Frontiers in oncology · 2024Pooled it
- Combining neoadjuvant chemotherapy with PD-1/PD-L1 inhibitors for locally advanced, resectable gastric or gastroesophageal junction adenocarcinoma: A systematic review and meta-analysis.Frontiers in oncology · 2023Pooled it
- Immune Checkpoint Inhibitors in the Treatment of Patients With Cancer and Preexisting Psoriasis: A Systematic Review and Meta-Analysis of Observational Studies.Frontiers in oncology · 2022Pooled it
- Treatment-Related Serious Adverse Events of Immune Checkpoint Inhibitors in Clinical Trials: A Systematic Review.Frontiers in oncology · 2021Pooled it
- The efficacy and safety of the addition of poly ADP-ribose polymerase (PARP) inhibitors to therapy for ovarian cancer: a systematic review and meta-analysis.World journal of surgical oncology · 2020Pooled it
- Quantitative Systems Pharmacology Model Predicts Enhanced Antitumor Efficacy of Combined Cytotoxic T‑Lymphocyte-Associated Protein 4 (CTLA-4) and Programmed Cell Death Protein 1 (PD-1) Blockade in a Syngeneic Mouse Model of Breast Cancer.ACS pharmacology & translational science · 2026Article
- Risk Factors for Cutaneous Immune-Related Adverse Events in the Japanese Population: A Retrospective Single-Center Cohort Study.The Journal of dermatology · 2026Article
- DMBX1 expression in colon cancer and its impact on prognosis and the tumor microenvironment.BMC medical genomics · 2026Article
- Risk Factors and Survival Outcomes of Immune Checkpoint Inhibitor-Induced Type 1 Diabetes Mellitus: A Retrospective Cohort Study.Diabetes & metabolism journal · 2026Article
- Assessing brain metastasis response to immunotherapy: a pictorial review of atypical responses and intracranial adverse events.Insights into imaging · 2025Article
- Lung adenocarcinoma-derived IFN-γ promotes growth by modulating CD8+ T cell production of CCR5 chemokines.The Journal of clinical investigation · 2025Article
- Cancer Immunotherapy in Combination with Radiotherapy and/or Chemotherapy: Mechanisms and Clinical Therapy.MedComm · 2025Review
- The real-world safety profile of pemetrexed and platinum with or without pembrolizumab: insights from a comparative analysis of FAERS database.BMC cancer · 2025Article
- Nutritional intervention alleviates T cell exhaustion and empowers anti-tumor immunity.Frontiers in immunology · 2025Review
- Regulatory T cells in immune checkpoint blockade antitumor therapy.Molecular cancer · 2024Review
- The Trend of the Treatment of Advanced Hepatocellular Carcinoma: Combination of Immunotherapy and Targeted Therapy.Current treatment options in oncology · 2024Review
- Immune-related Adverse Event with Checkpoint Inhibitors Might Be an Emerging Underlying Disease of Steroid-related Osteonecrosis of the Femoral Head: A Case Report.Journal of orthopaedic case reports · 2024Article
- Critical role of the gut microbiota in immune responses and cancer immunotherapy.Journal of hematology & oncology · 2024Review
- Update on Neuro-ophthalmic Manifestations of Immune Checkpoint Inhibitors.Current neurology and neuroscience reports · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe future of combined immunotherapy (a PD-1/PD-L1 plus a CTLA-4 antagonist) is very bright. However, besides improving efficacy, combined therapy increases treatment-related adverse events (TRAEs). Also, the clinical application is limited in some solid tumors.
methodsThis paper purports to investigate the TRAEs for the combined immunotherapy aiming for a more appropriate utilization of immune checkpoint inhibitors (ICIs) in clinical practice through a meta-analysis.
resultsA total of 17 eligible studies covering 2626 patients were selected for a meta-analysis based on specified inclusion and exclusion criteria. The incidence rates of any grade and grade 3 or higher TRAEs were 88% (95%CI, 84-92%) and 41% (95%CI, 35-47%), respectively. The overall incidence of any grade TRAEs leading to discontinuation of treatment was 20% (95%CI, 16-24%). The incidence rate of treatment related deaths was 4.3‰ (95%CI, 1.4‰-8.4‰). Analysis showed that NIVO1 + IPI3 cohort had higher incidences of grade 3 or higher TRAEs (RR = 1.77, 95%CI, 1.34-2.34, p < 0.0001) and any grade TRAEs leading to discontinuation of treatment (RR = 1.81, 95%CI, 1.08-3.04, P = 0.02), compared with NIVO3 + IPI1 regimen.
conclusionsThe combined therapy had high TRAEs. The TRAEs, especially grade 3 or higher, led to discontinuation of the treatment. Furthermore, the incidence of treatment-related deaths was rare. Moreover, the NIVO3 + IPI1 regimen, regardless of efficacy, is more recommended because of better tolerance and lower adverse events.
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Registered trials
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.