SynthesisTargeted oncology2026
Time-Dependent Comparative Effectiveness of First-Line Treatment for Metastatic Clear Cell Renal Cell Carcinoma: A Restricted Mean Survival Time-Based Network Meta-analysis.
Synthesis in Targeted oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers, 1 of them a synthesis 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
4 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Real-World Comparative Effectiveness and Safety of Immune Checkpoint Inhibitors in Advanced Renal Cell Carcinoma: A Systematic Review.Targeted oncology · 2026Pooled it
- POU2F2 as a dual oncogenic and immunomodulatory driver in kidney renal clear cell carcinoma.Cell adhesion & migration · 2026Article
- From trial results to bedside decisions: a time-resolved view of CheckMate-9ER.Translational andrology and urology · 2026Article
- Case Report: No radiographic evidence of disease for 45 months in a patient with recurrent clear cell renal cell carcinoma treated with third-line combination therapy utilizing toripalimab and axitinib.Frontiers in immunology · 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
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundGiven that immune checkpoint inhibitor-based regimens frequently yield delayed separation and late plateaus, conventional hazard ratio analyses that assume proportional hazards may misstate true benefit.
objectiveWe aimed to test the validity of the proportional hazards assumption in first-line metastatic clear cell renal cell carcinoma trials and to compare the immune checkpoint inhibitor-based regimens using restricted mean survival time.
methodsWe performed a systematic review and network meta-analysis of phase III randomized controlled trials of first-line treatment for metastatic clear cell renal cell carcinoma, including immune checkpoint inhibitor-tyrosine kinase inhibitor combinations or dual-immune checkpoint inhibitor regimens. Individual patient data were reconstructed from the Kaplan-Meier curves of overall survival and progression-free survival. The restricted mean survival time differences were estimated.
resultsFive trials (4206 patients; six treatment arms) were examined. Proportional hazards assumption was violated in 60% of both overall survival and progression-free survival comparisons. In the restricted mean survival time-based network meta-analysis of overall survival, immune checkpoint inhibitor-tyrosine kinase inhibitor combinations, especially Nivolumab + Cabozantinib, dominated at 12-48 months, whereas Ipilimumab + Nivolumab ranked highest beyond 48 months. In the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) favorable-risk subgroup, Avelumab + Axitinib showed a favorable long-term profile despite the lack of statistical significance. In IMDC intermediate/poor-risk, patterns mirrored the overall population. For progression-free survival, Pembrolizumab + Lenvatinib ranked best across IMDC subgroups. Limitations included the reliance on reconstructed data and heterogeneity across trials.
conclusionsGiven the frequent proportional hazards violations, hazard ratio-only syntheses are insufficient for modern immune checkpoint inhibitor-based regimens. In the restricted mean survival time-based network meta-analysis, Pembrolizumab + Lenvatinib delivered rapid disease control, and Ipilimumab + Nivolumab showed the greatest late survival advantage in IMDC intermediate/poor-risk. PROSPERO REGISTRATION NUMBER: CRD420251143602.
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Identifiers
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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.