ReviewEXCLI journal2026
Efficacy and safety of CTLA-4, PD-1 and LAG-3 immune checkpoint inhibitors as monotherapy and combination therapy in advanced melanoma: A systematic review and meta-analysis.
Review in EXCLI journal, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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.
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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
2 citing papers in PubMed.
- Landscape of T-cell bispecific antibodies in cancer therapy: therapeutic strategies, challenges and future prospection.Molecular cancer · 2026Review
- Sustained metabolic response in metastatic melanoma after intraperitoneal ozone therapy: a case report.AME case reports · 2026Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
1 author.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Advanced unresectable melanoma carries a poor prognosis, with minimal benefit from chemotherapy and limited responsiveness to radiotherapy. The emergence of immune checkpoint inhibitors (ICIs) targeting PD-1, CTLA-4, and LAG-3 has transformed treatment outcomes; however, their comparative efficacy and safety remain unclear. This systematic review and meta-analysis evaluated and compared the efficacy and safety of PD-1 and CTLA-4 monotherapies against traditional systemic therapies, as well as the dual regimens PD-1 + CTLA-4 and PD-1 + LAG-3 against their respective monotherapies, in patients with advanced unresectable melanoma. A comprehensive search of PubMed and the Cochrane CENTRAL database was conducted on March 18, 2025, for randomized controlled trials comparing ICIs against conventional therapies or other ICI regimens. Primary endpoints included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and grade ≥ 3 adverse events (AEs). A random-effects meta-analysis was performed, and risk of bias was assessed using the Cochrane RoB 2.0 tool. Eleven randomized controlled trials (n = 4,111) met the inclusion criteria. The PD-1 + CTLA-4 combination demonstrated the greatest clinical benefit, significantly improving OS (HR = 0.59), PFS (HR = 0.45), and ORR (RR = 3.11) compared with monotherapy, but was associated with a higher incidence of grade ≥ 3 AEs (RR = 2.14). The PD-1 + LAG-3 regimen showed a moderate yet statistically significant advantage in efficacy over PD-1 monotherapy (OS HR = 0.80) while maintaining better tolerability. PD-1 monotherapy demonstrated greater efficacy and a more favorable safety profile than CTLA-4 monotherapy when each was compared with traditional therapy. In conclusion, PD-1 + CTLA-4 offers the most substantial therapeutic improvement but with considerable toxicity, whereas PD-1 + LAG-3 provides a more balanced efficacy-safety profile. PD-1 monotherapy remains the safest option, though less effective than combination strategies. These findings highlight the evolving role of combination immunotherapies and the potential clinical value of LAG-3 as a novel checkpoint target in melanoma management. See also the graphical abstract(Fig. 1).
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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 Socratic graph.