Efficacy of immune-oncology combinations versus sunitinib in patients with bone metastases from renal cell carcinoma: A systematic review and meta-analysis of phase III trials with long-term follow-up.
6 affiliations
- 1Interdisciplinary Department of Medicine, University of Bari "Aldo Moro", Bari, Italy.
- 2Division of Medical Oncology, Azienda Ospedaliero-Universitaria Consorziale Policlinico di Bari, Bari, Italy.
- 3University of São Paulo, São Paulo, Brazil.
- 4Unimed Sorocaba, Sorocaba, Brazil.
- 5Barretos Cancer Hospital (Hospital de Amor), Barretos, São Paulo, Brazil.
- 6Universidade Regional de Blumenau (FURB), Blumenau, Brazil.
Abstract
Background
Bone metastases occur in approximately one-third of patients with metastatic clear-cell renal cell carcinoma (ccRCC) and are associated with poor prognosis. Although immune-oncology (IO)-based combinations are the standard first-line treatment, the relative efficacy of IO plus tyrosine kinase inhibitor (IO+TKI) versus dual immunotherapy (IO+IO) in this subgroup remains uncertain.Methods
We performed a systematic review and meta-analysis of phase III randomized trials comparing first-line IO-based combinations with sunitinib in treatment-naïve metastatic ccRCC. Eligible studies reported hazard ratios (HRs) for progression-free survival (PFS) and/or overall survival (OS) in patients with baseline bone metastases and had a median follow-up of at least 36 months. The primary analysis pooled IO+TKI trials, whereas the single eligible IO+IO study was analyzed separately. Fixed- and random-effects inverse-variance models were applied.Results
Three phase III trials were included: CLEAR (lenvatinib plus pembrolizumab versus sunitinib), CheckMate 9ER (nivolumab plus cabozantinib versus sunitinib), and CheckMate 214 (nivolumab plus ipilimumab versus sunitinib). IO+TKI significantly improved PFS versus sunitinib (HR 0.46, 95% CI 0.35-0.61; p < 0.0001), with no heterogeneity (I² = 0%). In contrast, IO+IO showed no PFS benefit (HR 1.07, 95% CI 0.76-1.51). Pooling all trials introduced substantial heterogeneity (I² = 85.9%), and subgroup analysis confirmed a significant interaction between treatment class and PFS (p = 0.0002). IO+TKI also improved OS (HR 0.66, 95% CI 0.50-0.88; p = 0.0041), again without heterogeneity (I² = 0%). IO+IO showed a non-significant trend toward improved OS (HR 0.82, 95% CI 0.61-1.11), with no significant difference between treatment classes for OS (p = 0.314).Conclusions
In patients with metastatic ccRCC and bone metastases, IO+TKI combinations were associated with significant improvements in PFS and OS compared with sunitinib, whereas IO+IO did not improve PFS. These findings suggest that treatment strategy may influence outcomes in this high-risk subgroup.
Related
- Comparative efficacy of common adjuvant treatments after resection of colorectal liver metastases : A systematic review and network meta-analysis
- Central nervous system efficacy of third generation vs. first generation EGFR-TKIs in the first line treatment for EGFR-mutated non-small cell lung cancer with central nervous system metastases: a systematic review and meta-analysis of phase 3 randomized controlled trials
- The KLF4–SLC25A4 mitochondrial axis regulates ferroptotic vulnerability and sunitinib sensitivity in clear cell renal cell carcinoma
- Culture Dimensionality Shapes Drug Sensitivity to Kinase Inhibitor Combinations with Epigenetic or Metabolic Inhibition in a Hepatocellular Carcinoma Model
- Efficacy and safety of first- versus second-generation fibroblast growth factor receptor (FGFR) inhibitors in advanced or metastatic urothelial carcinoma with FGFR alterations: a systematic review and meta-analysis
BibTeX
@article{albuquerque2026efficacy,
title = {{Efficacy of immune-oncology combinations versus sunitinib in patients with bone metastases from renal cell carcinoma: A systematic review and meta-analysis of phase III trials with long-term follow-up.}},
author = {Clara Fish Araujo de Albuquerque and Leila Caroline Souza Reis and Eliza Del Fiol Manna and Ana Elisa Saragossa Zafalon and Angela Theresa Zuffo Yabrude and Camillo Porta},
journal = {Journal of bone oncology},
year = {2026},
month = oct,
doi = {10.1016/j.jbo.2026.100806},
url = {https://europepmc.org/article/MED/42898627},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Efficacy of immune-oncology combinations versus sunitinib in patients with bone metastases from renal cell carcinoma: A systematic review and meta-analysis of phase III trials with long-term follow-up.
AU - Clara Fish Araujo de Albuquerque
AU - Leila Caroline Souza Reis
AU - Eliza Del Fiol Manna
AU - Ana Elisa Saragossa Zafalon
AU - Angela Theresa Zuffo Yabrude
AU - Camillo Porta
PY - 2026
DA - 2026/10/07
JO - Journal of bone oncology
DO - 10.1016/j.jbo.2026.100806
UR - https://europepmc.org/article/MED/42898627
AB - Background Bone metastases occur in approximately one-third of patients with metastatic clear-cell renal cell carcinoma (ccRCC) and are associated with poor prognosis. Although immune-oncology (IO)-based combinations are the standard first-line treatment, the relative efficacy of IO plus tyrosine kinase inhibitor (IO+TKI) versus dual immunotherapy (IO+IO) in this subgroup remains uncertain.Methods We performed a systematic review and meta-analysis of phase III randomized trials comparing first-line IO-based combinations with sunitinib in treatment-naïve metastatic ccRCC. Eligible studies reported hazard ratios (HRs) for progression-free survival (PFS) and/or overall survival (OS) in patients with baseline bone metastases and had a median follow-up of at least 36 months. The primary analysis pooled IO+TKI trials, whereas the single eligible IO+IO study was analyzed separately. Fixed- and random-effects inverse-variance models were applied.Results Three phase III trials were included: CLEAR (lenvatinib plus pembrolizumab versus sunitinib), CheckMate 9ER (nivolumab plus cabozantinib versus sunitinib), and CheckMate 214 (nivolumab plus ipilimumab versus sunitinib). IO+TKI significantly improved PFS versus sunitinib (HR 0.46, 95% CI 0.35-0.61; p < 0.0001), with no heterogeneity (I² = 0%). In contrast, IO+IO showed no PFS benefit (HR 1.07, 95% CI 0.76-1.51). Pooling all trials introduced substantial heterogeneity (I² = 85.9%), and subgroup analysis confirmed a significant interaction between treatment class and PFS (p = 0.0002). IO+TKI also improved OS (HR 0.66, 95% CI 0.50-0.88; p = 0.0041), again without heterogeneity (I² = 0%). IO+IO showed a non-significant trend toward improved OS (HR 0.82, 95% CI 0.61-1.11), with no significant difference between treatment classes for OS (p = 0.314).Conclusions In patients with metastatic ccRCC and bone metastases, IO+TKI combinations were associated with significant improvements in PFS and OS compared with sunitinib, whereas IO+IO did not improve PFS. These findings suggest that treatment strategy may influence outcomes in this high-risk subgroup.
SN - 2212-1366
SN - 2212-1374
ER -