Efficacy and safety of immunotherapy-based combination therapy as first-line treatment for advanced renal cell carcinoma: a systematic review and network meta-analysis
In brief
Pembrolizumab-lenvatinib cuts death risk by about 43% in advanced kidney cancer
A network meta-analysis of 14 studies (6,193 patients) found that pembrolizumab plus lenvatinib reduced overall mortality by roughly 43% compared with other first-line immunotherapy combos, and showed the best progression-free survival among all-risk groups. The regimen was less well tolerated than nivolumab-ipilimumab, and the findings need confirmation because of limited trial numbers and methodological heterogeneity.
- Journal
- Medical oncology (Northwood, London, England) (Q1)
- Published
- 22 July 2026
- Study design
- Systematic review / meta-analysis of RCTs
- Evidence level
- Level 1, High (CEBM 1a)
- Authors
- Xiaoyu Ou, Yan Li, Mengru Zhan, Tiantian Tao, Pingyu Chen
- PMID
- 42484760
- DOI
- 10.1007/s12032-026-03343-1
Why clinicians should know about it
- Picked for Oncology and Radiation Oncology (top studies of the week, 27 July 2026): Systematic review & network meta‑analysis of first‑line immunotherapy combos in
- Picked for Hematology (top studies of the week, 26 July 2026): Recent Hematology research from a high-quartile journal.
- Picked for Immunology and Allergy (top studies of the week, 26 July 2026).
- Picked for Nephrology (top studies of the week, 26 July 2026).
- Picked for Urology (top studies of the week, 26 July 2026): Immunotherapy combos improve OS/PFS in advanced RCC
Abstract
To update a network meta-analysis of first-line immunotherapy combinations in advanced renal cell carcinoma (RCC) using short-term data for primary analysis and long-term plus newly published randomized controlled trials (RCTs) for subgroup analyses. We searched PubMed, Embase, Web of Science, Cochrane Library, and Chinese databases for articles from inception to 22 December 2024, performing a Bayesian network meta-analysis. Overall survival (OS), progression-free survival (PFS), objective response rates (ORR), and adverse events (AEs) were assessed using hazard ratios (HRs) and odds ratios (OR) in all-risk and intermediate- and poor-risk subgroups. Fourteen articles and nine RCTs involving 6,193 patients and nine regimens were included. Pembrolizumab plus axitinib (HR: 0.57, 95% CI: 0.39-0.84) improved OS compared to atezolizumab plus bevacizumab. Pembrolizumab plus lenvatinib (HR: 0.57, 95% CI: 0.42-0.76) showed superior PFS to pembrolizumab plus axitinib with comparable efficacy to nivolumab plus cabozantinib (HR: 1.31, 95% CI: 0.96-1.78) and higher ORR versus pembrolizumab plus axitinib (OR: 0.61, 95% CI: 0.39-0.92). Rank probabilities identified pembrolizumab plus axitinib and pembrolizumab plus lenvatinib as optimal regimens in all-risk populations. Subgroup analyses prioritized pembrolizumab plus lenvatinib (PFS: 98.8%), toripalimab plus axitinib (OS: 77.3%), and pembrolizumab plus axitinib (ORR: 94.9%) for intermediate- and poor-risk patients. Conclusions require validation due to limited trials and methodological heterogeneity. In the first-line treatment of advanced RCC, pembrolizumab plus lenvatinib enhances survival with poorer safety versus nivolumab plus ipilimumab's improved tolerability. Toripalimab plus axitinib may be associated with relatively greater efficacy in intermediate- and poor-risk patients.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.