Bone metastases negatively affect prognosis in patients with advanced renal cell carcinoma (aRCC). We conducted a systematic literature review to identify clinical trial publications including patients with aRCC with and without bone metastases.
The review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta‑Analyses (PRISMA) guidelines and registered with PROSPERO (CRD42022355436). MEDLINE and Embase databases were searched (September 2, 2022) to identify publications reporting efficacy and safety outcomes for patients with/without bone metastasis from clinical trials of systemic RCC therapies. Risk of bias was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE).
Of 526 publications screened, 19 were eligible: seven (from five studies) reported phase 3 trials, six reported phase 2 trials, one reported phase 1b/2 trials, and five were pooled analyses. Five publications reported moderate-quality evidence, while 14 were graded as low- or very low-quality evidence, suggesting a high potential for uncertainty. Five studies reported benefits of investigational therapies versus comparators in patients with and without bone metastases; these studies included cabozantinib, nivolumab, cabozantinib plus nivolumab, and lenvatinib plus pembrolizumab treatment arms. Data were also available for nivolumab plus ipilimumab. Bone metastases were consistently associated with poor prognosis in patients with aRCC. Preliminary data support the hypothesis that therapies targeting pathways implicated in the development of bone metastases may be beneficial, and warrant further investigation. However, data to support treatment decision-making are lacking.
Our findings highlight the need for clinical data to assist in defining the optimal treatment for patients with aRCC and bone metastasis.
Cancer treatment reviews. 2024 Jun 26 [Epub ahead of print]
Janet Brown, Daniele Santini, Natalie Charnley, Alessia Ogareva, Alison Chisholm, Robert Jones
Division of Clinical Medicine, University of Sheffield, Sheffield, UK. Electronic address: ., Medical Oncology A, Policlinico Umberto 1, La Sapienza University of Rome, Italy., Lancashire Teaching Hospitals, Cancer Services, Preston, UK., Ipsen, Boulogne-Billancourt, France., Oxford PharmaGenesis, Oxford, UK., School of Cancer Sciences, University of Glasgow, Glasgow, UK.