Saved0Subscribe
OncologyMeta-analysis

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

Journal of bone oncology · 7 Oct 2026

Rigour42/100
Clinical48/100
Impact†53/100

† Impact is the editorial-priority score. All scores are out of 100. Clinical is a stored clinical-importance score from the earlier method; it has not been recalculated.

Why it matters

Bone metastases are common in kidney cancer and carry a poor prognosis, so the choice of systemic therapy shapes survival in patients an orthopaedic surgeon may be asked to stabilize or fix.

The evidence

This meta-analysis pooled the bone-metastasis subgroups of three phase III trials (CLEAR, CheckMate 9ER, CheckMate 214) in untreated metastatic clear-cell kidney cancer that compared immunotherapy-based combinations with sunitinib. In the two trials that paired an immune checkpoint inhibitor with a VEGF tyrosine kinase inhibitor (IO+TKI), the risk of progression was roughly halved (pooled HR 0.46, 95% CI 0.35 to 0.61) and the risk of death was lower (HR 0.66, 95% CI 0.50 to 0.88). The single dual-immunotherapy trial (nivolumab plus ipilimumab) showed no clear PFS benefit (HR 1.07) and a non-significant OS trend (HR 0.82).

Progression-free survival in the bone-metastasis subgroup: Hazard ratio 0.46 (95% CI 0.35 to 0.61; ratio). The interval favours the first group; the size of the benefit needs clinical interpretation.

Why this rigour score?

Meta-analysis of RCTsDesign starting point: 60.8

42/ 100

Raised the score

  • Prospectively registered+5.1
  • Pools randomised trials+5.1

Lowered the score

  • Outdated comparator−8.5

Score capped at 42. Two or more critical methodological failures for a review.

Methods at a glance

Recorded assessment
  • Comprehensive literature searchMet
  • Risk of bias assessedNot met
  • Bias considered in synthesisNot met
  • Publication bias assessedMet
  • Study exclusions justifiedMet
  • Prospective registrationMet

Not reported does not mean not done. Checks have different weights; this is not a count of boxes ticked.

See the full score breakdown
Study design starting point
60.8
Outdated comparator
−8.5
Prospectively registered
+5.1
Pools randomised trials
+5.1
Comprehensive literature search
+3.4
Excluded studies listed and justified
+1.7
Publication bias assessed
+2.5
Methodological cap
−28.1
Final rigour score rounded
42 / 100

Study design sets the starting point and a ceiling of 96. Recorded methods then adjust the score. Points are shown to one decimal place; the final score uses unrounded values.

Checklist from the stored appraisal. “Not met” describes the recorded criterion; it does not always produce a deduction. This overview supports reading the full study.

For journal club

1.For a patient with metastatic clear-cell RCC presenting with a pathologic fracture or impending fracture, how should the expected survival with IO+TKI therapy influence the choice between durable reconstruction (such as endoprosthesis) and simpler fixation?

2.How should the orthopaedic and oncology teams coordinate timing of surgery, radiotherapy, and bone-targeted agents around starting an IO+TKI regimen, given that VEGF inhibitors can impair wound healing?

Original publication 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

Read original paper