---
title: "Safety profiles of PD-1/CTLA-4 and PD-1/VEGF bispecific antibodies in NSCLC: pooled systematic rev"
id: "pubmed-42554769"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42554769"
content_type: "clinical_feed_article"
specialty: "Oncology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42554769/"
doi: "10.1186/s43046-026-00387-2"
published_at: "2026-08-05T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Safety profiles of PD-1/CTLA-4 and PD-1/VEGF bispecific antibodies in NSCLC: pooled systematic rev
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42554769
- **Specialty:** [Oncology](https://medichelpline.com/clinical-feed/oncology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42554769/)
- **DOI:** [10.1186/s43046-026-00387-2](https://doi.org/10.1186%2Fs43046-026-00387-2)
- **Published At:** 2026-08-05T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- This systematic review and single-arm meta-analysis pooled safety data for bispecific antibodies (BsAbs) targeting **PD-1/CTLA-4** and **PD-1/VEGF** in patients with non-small cell lung cancer (**NSCLC**). - The authors followed PRISMA guidance and included 17 prospective clinical trials published through January 2026, comprising 1,802 patients across cohorts. - Single-arm proportion meta-analyses using random-effects models were performed separately for each BsAb class; no formal statistical comparison between classes was conducted. - Pooled incidence of grade ≥3 treatment-related adverse events (**TRAEs**) was 41.79% for PD-1/CTLA-4 BsAbs and 43.51% for PD-1/VEGF BsAbs. - Pooled treatment discontinuation due to TRAEs was 10.26% for PD-1/CTLA-4 and 4.44% for PD-1/VEGF cohorts. - Pooled incidence of immune-related adverse events (**irAEs**) was 46.68% in the PD-1/CTLA-4 analysis and 27.10% in the PD-1/VEGF analysis; pooled rates of grade ≥3 irAEs were low for both classes. - Exploratory subgroup findings suggested heterogeneity: AE rates varied by individual agent within PD-1/CTLA-4 studies and were higher in chemotherapy-containing regimens among PD-1/VEGF studies. - The authors caution that observed differences may reflect heterogeneity in study phase, treatment line, molecular subtypes, agents, and concomitant therapies rather than intrinsic class toxicity. - Because cohorts differed substantially across multiple characteristics, pooled estimates are presented descriptively and intended as hypothesis-generating signals for more homogeneous or head-to-head studies. - The report declares no competing interests and notes ethics approval and consent for publication were not applicable.
## Clinical Analysis & Structured Key Points
Pooled safety profiles of bispecific antibodies targeting PD-1/CTLA-4 or PD-1/VEGF in non-small cell lung cancer: a systematic review and single-arm meta-analysis - PubMed This site needs JavaScript to work properly. Please enable it to take advantage of the complete set of features! Clipboard, Search History, and several other advanced features are temporarily unavailable. Skip to main page content The .gov means it’s official. Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site. The site is secure. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely. Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation Search: Search Advanced Clipboard User Guide Save Email Send to Clipboard My Bibliography Collections Citation manager Display options Display options Format Abstract PubMed PMID Save citation to file Format: Summary (text) PubMed PMID Abstract (text) CSV Create file Cancel Email citation Email address has not been verified. Go to My NCBI account settings to confirm your email and then refresh this page. To: Subject: Body: Format: Summary Summary (text) Abstract Abstract (text) MeSH and other data Send email Cancel Add to Collections Create a new collection Add to an existing collection Name your collection: Name must be less than 100 characters Choose a collection: Unable to load your collection due to an error Please try again Add Cancel Add to My Bibliography My Bibliography Unable to load your delegates due to an error Please try again Add Cancel Your saved search Name of saved search: Search terms: Test search terms Would you like email updates of new search results? Saved Search Alert Radio Buttons Yes No Email: ( change ) Frequency: Monthly Weekly Daily Which day? The first Sunday The first Monday The first Tuesday The first Wednesday The first Thursday The first Friday The first Saturday The first day The first weekday Which day? Sunday Monday Tuesday Wednesday Thursday Friday Saturday Report format: Summary Summary (text) Abstract Abstract (text) PubMed Send at most: 1 item 5 items 10 items 20 items 50 items 100 items 200 items Send even when there aren't any new results Optional text in email: Save Cancel Create a file for external citation management software Create file Cancel Your RSS Feed Name of RSS Feed: Number of items displayed: 5 10 15 20 50 100 Create RSS Cancel RSS Link Copy Actions Cite Collections Add to Collections Create a new collection Add to an existing collection Name your collection: Name must be less than 100 characters Choose a collection: Unable to load your collection due to an error Please try again Add Cancel Permalink Permalink Copy Display options Display options Format Abstract PubMed PMID Cite Display options Display options Format Abstract PubMed PMID Abstract Objective: This study aimed to systematically synthesize and separately quantify the pooled safety profiles of bispecific antibodies (BsAbs) targeting PD-1/CTLA-4 or PD-1/VEGF in patients with non-small cell lung cancer (NSCLC), and to descriptively summarize class-specific safety patterns. Methods: Following PRISMA guidelines, we systematically reviewed prospective clinical trials published through January 2026. A total of 17 studies, encompassing 1802 patients, were included. Single-arm proportion meta-analyses were conducted separately for each BsAb class using random-effects models. No formal between-class statistical comparison was performed. Given the clinical heterogeneity across included cohorts, including differences in study phase, treatment line, molecular subtype, and treatment regimen, pooled estimates were interpreted descriptively. Subgroup analyses by treatment regimen, treatment line, and individual BsAb agent were considered exploratory. Because of the limited number of cohorts within each phase stratum, the impact of study phase was assessed descriptively rather than through formal stratified meta-analysis. Results: In separate pooled analyses, the incidence of grade 3 or higher treatment-related adverse events (TRAEs) was 41.79% for PD-1/CTLA-4 BsAbs and 43.51% for PD-1/VEGF BsAbs. Exploratory subgroup analyses suggested different patterns of heterogeneity across the available cohorts. In PD-1/CTLA-4 BsAb studies, AE rates appeared to vary across individual agents, whereas in PD-1/VEGF BsAb studies, higher AE rates were observed mainly in chemotherapy-containing regimens. These observations should be interpreted cautiously because they may reflect differences in the distribution of included agents, patient populations, study phases, and treatment strategies rather than inherent class-specific toxicity mechanisms. Regarding tolerability, the pooled treatment discontinuation rate due to TRAEs was 10.26% in the PD-1/CTLA-4 analysis and 4.44% in the PD-1/VEGF analysis. The pooled incidence of immune-related adverse events (irAEs) was 46.68% in the PD-1/CTLA-4 analysis and 27.10% in the PD-1/VEGF analysis, whereas the pooled rates of grade 3 or higher irAEs were low in both analyses. Conclusion: This systematic review provides a descriptive synthesis of available safety data for PD-1/CTLA-4 and PD-1/VEGF BsAbs in NSCLC. Because the included cohorts differed substantially in study phase, treatment line, molecular background, and concomitant therapies, the pooled AE estimates should not be interpreted as direct comparative evidence. Instead, the findings should be viewed as hypothesis-generating signals that require validation in more homogeneous prospective studies or head-to-head trials. Keywords: Bispecific antibodies; Meta-analysis; Non-small cell lung cancer (NSCLC); PD-1/CTLA-4; PD-1/VEGF; Safety. © 2026. The Author(s). PubMed Disclaimer Conflict of interest statement Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. References Luo G, Zhang Y, Rumgay H, Morgan E, Langselius O, Vignat J, Colombet M, Bray F. Estimated worldwide variation and trends in incidence of lung cancer by histological subtype in 2022 and over time: a population-based study. Lancet Respir Med. 2025;13(4):348–63. - DOI - PubMed Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. Cancer J Clin. 2021;71(3):209–49. - DOI Pauken KE, Dougan M, Rose NR, Lichtman AH, Sharpe AH. Adverse Events Following Cancer Immunotherapy: Obstacles and Opportunities. Trends Immunol. 2019;40(6):511–23. - DOI - PubMed - PMC Ephraim R, Fraser S, Nurgali K, Apostolopoulos V. Checkpoint markers and tumor microenvironment: What do we know? Cancers (Basel). 2022;14(15):3788. https://doi.org/10.3390/cancers14153788 . Garassino MC, Gadgeel S, Speranza G, Felip E, Esteban E, Dómine M, Hochmair MJ, Powell SF, Bischoff HG, Peled N, et al. Pembrolizumab Plus Pemetrexed and Platinum in Nonsquamous Non-Small-Cell Lung Cancer: 5-Year Outcomes From the Phase 3 KEYNOTE-189 Study. J Clin Oncol. 2023;41(11):1992–8. - DOI - PubMed - PMC Show all 54 references Publication types Systematic Review Actions Search in PubMed Search in MeSH Add to Search Meta-Analysis Actions Search in PubMed Search in MeSH Add to Search MeSH terms Antibodies, Bispecific* / adverse effects Actions Search in PubMed Search in MeSH Add to Search Antibodies, Bispecific* / therapeutic use Actions Search in PubMed Search in MeSH Add to Search CTLA-4 Antigen* / antagonists & inhibitors Actions Search in PubMed Search in MeSH Add to Search CTLA-4 Antigen* / immunology Actions Search in PubMed Search in MeSH Add to Search Carcinoma, Non-Small-Cell Lung* / drug therapy Actions Search in PubMed Search in MeSH Add to Search Carcinoma, Non-Small-Cell Lung* / immunology Actions Search in PubMed Search in MeSH Add to Search Carcinoma, Non-Small-Cell Lung* / pathology Actions Search in PubMed Search in MeSH Add to Search Humans Actions Search in PubMed Search in MeSH Add to Search Immune Checkpoint Inhibitors* / adverse effects Actions Search in PubMed Search in MeSH Add to Search Immune Checkpoint Inhibitors* / therapeutic use Actions Search in PubMed Search in MeSH Add to Search Lung Neoplasms* / drug therapy Actions Search in PubMed Search in MeSH Add to Search Lung Neoplasms* / immunology Actions Search in PubMed Search in MeSH Add to Search Lung Neoplasms* / pathology Actions Search in PubMed Search in MeSH Add to Search Programmed Cell Death 1 Receptor* / antagonists & inhibitors Actions Search in PubMed Search in MeSH Add to Search Programmed Cell Death 1 Receptor* / immunology Actions Search in PubMed Search in MeSH Add to Search Vascular Endothelial Growth Factor A* / antagonists & inhibitors Actions Search in PubMed Search in MeSH Add to Search Vascular Endothelial Growth Factor A* / immunology Actions Search in PubMed Search in MeSH Add to Search Substances Programmed Cell Death 1 Receptor Actions Search in PubMed Search in MeSH Add to Search Antibodies, Bispecific Actions Search in PubMed Search in MeSH Add to Search CTLA-4 Antigen Actions Search in PubMed Search in MeSH Add to Search Vascular Endothelial Growth Factor A Actions Search in PubMed Search in MeSH Add to Search PDCD1 protein, human Actions Search in PubMed Search in MeSH Add to Search Immune Checkpoint Inhibitors Actions Search in PubMed Search in MeSH Add to Search CTLA4 protein, human Actions Search in PubMed Search in MeSH Add to Search VEGFA protein, human Actions Search in PubMed Search in MeSH Add to Search [x] Cite Copy Download .nbib .nbib Format: AMA APA MLA NLM Send To Clipboard Email Save My Bibliography Collections Citation Manager [x] NCBI Literature Resources MeSH PMC Bookshelf Disclaimer The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.
## Related Clinical Research

- [Translational modelling questions receptor‑occupancy‑based dosing for pembrolizumab (PD‑1 inhibito](https://medichelpline.com/clinical-feed/british-journal-of-cancer-0-translational-modelling-challenges-receptor-occupancy-based-dosing-of-pd-1.md)
- [PD-L1 expression and survival in unresectable or recurrent gastric cancer treated with first-line](https://medichelpline.com/clinical-feed/british-journal-of-cancer-0-pd-l1-expression-and-survival-in-unresectable-recurrent-gastric-cancer-treated.md)
- [Oncolytic Virotherapy: Evolving from Cold-to-Hot to a Foundational Immuno‑Oncology Platform](https://medichelpline.com/clinical-feed/nature-reviews-clinical-oncology-0-beyond-cold-to-hot-oncolytic-virotherapy-as-the-next-cornerstone-of-immuno.md)
- [Challenging FDA-Approved Cancer Drug Dosages: A Patient and Research Perspective](https://medichelpline.com/clinical-feed/kff-health-news-2-how-much-of-a-cancer-drug-is-too-much-patients-researchers-challenge-fda.md)
- [Chemotherapy and Immunotherapy Dosing in Congenital Achondroplasia: Case Report and Review](https://medichelpline.com/clinical-feed/pubmed-42545505.md) (DOI: 10.1007/s00280-026-04932-7)

## Navigation
- [← Back to Oncology Feed](https://medichelpline.com/clinical-feed/oncology.md)
- [← All Clinical Specialties](https://medichelpline.com/clinical-feed.md)
## Medical & Regulatory Disclaimer

> [!CAUTION]
> MedicHelpline content is structured for research, educational, and professional discovery purposes. It does not constitute individual medical advice, clinical diagnosis, or treatment recommendations.
> Always verify dosing, contraindications, and regulatory alerts against official product labeling and primary regulatory sources before clinical decision-making.