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Updated: Jan 28, 2026
Modeling Spontaneous Metastatic Renal Cell Carcinoma mRCC in Mice Following Nephrectomy
Published on: April 29, 2014
Targeted therapies for previously treated advanced or metastatic renal cell carcinoma: systematic review and network
Charlotta Karner1, Kayleigh Kew1, Victoria Wakefield1
1British Medical Journal Technology Assessment Group (BMJ-TAG), BMA House, London, UK.
Objective:
To compare the effectiveness and safety of treatments for advanced or metastatic renal cell carcinoma (amRCC) after treatment with vascular endothelial growth factor (VEGF)-targeted treatment.
Design:
Systematic review and network meta-analysis of randomised controlled trials (RCTs) and comparative observational studies. MEDLINE, EMBASE and Cochrane Library were searched up to January 2018.
Participants:
People with amRCC requiring treatment after VEGF-targeted treatment.
Interventions:
Axitinib, cabozantinib, everolimus, lenvatinib with everolimus, nivolumab, sorafenib and best supportive care (BSC).
Outcomes:
Primary outcomes were overall survival (OS) and progression-free survival (PFS); secondary outcomes were objective response rate (ORR), adverse events, and health-related quality of life (HRQoL).
Results:
Twelve studies were included (n=5144): five RCTs and seven observational studies. Lenvatinib with everolimus significantly increased OS and PFS over everolimus (HR 0.61, 95% Credible Interval [95%CrI]: 0.36 to 0.96 and 0.47, 95%CrI: 0.26 to 0.77, respectively) as did cabozantinib (HR 0.66, 95%CrI: 0.53 to 0.82 and 0.51, 95%CrI: 0.41 to 0.63, respectively). This remained the case when observational evidence was included. Nivolumab also significantly improved OS versus everolimus (HR 0.74, 95%CrI: 0.57 to 0.93). OS sensitivity analysis, including observational studies, indicates everolimus being more effective than axitinib and sorafenib. However, inconsistency was identified in the OS sensitivity analysis. PFS sensitivity analysis suggests axitinib is more effective than everolimus, which may be more effective than sorafenib. The results for ORR supported the OS and PFS analyses. Nivolumab is associated with fewer grade 3 or grade 4 adverse events than lenvatinib with everolimus or cabozantinib. HRQoL could not be analysed due to differences in tools used.
Conclusions:
Lenvatinib with everolimus, cabozantinib and nivolumab are effective in prolonging the survival for people with amRCC subsequent to VEGF-targeted treatment, but there is considerable uncertainty about how they compare to each other and how much better they are than axitinib and sorafenib.
Prospero Registration Number:
CRD42017071540.
Insights
New treatments like lenvatinib with everolimus, cabozantinib, and nivolumab show promise for advanced renal cell carcinoma (amRCC) after VEGF-targeted therapy. However, direct comparisons and superiority over older treatments remain uncertain.
Area of Science:
- Oncology
- Medical Treatments
- Clinical Research
Background:
- Advanced or metastatic renal cell carcinoma (amRCC) poses significant treatment challenges.
- Vascular endothelial growth factor (VEGF)-targeted therapies are a standard first-line treatment for amRCC.
- Identifying effective subsequent treatment options is crucial for improving patient outcomes.
Purpose of the Study:
- To compare the effectiveness and safety of various treatments for amRCC following VEGF-targeted therapy.
- To synthesize evidence from randomized controlled trials (RCTs) and observational studies.
- To inform clinical decision-making for patients progressing after initial treatment.
Main Methods:
- Systematic review and network meta-analysis of RCTs and comparative observational studies.
- Searched MEDLINE, EMBASE, and Cochrane Library up to January 2018.
- Included studies involving patients with amRCC requiring treatment after VEGF-targeted therapy.
Main Results:
- Lenvatinib plus everolimus and cabozantinib significantly improved overall survival (OS) and progression-free survival (PFS) compared to everolimus alone.
- Nivolumab also demonstrated a significant improvement in OS versus everolimus.
- Nivolumab was associated with fewer severe adverse events compared to lenvatinib/everolimus and cabozantinib.
Conclusions:
- Lenvatinib/everolimus, cabozantinib, and nivolumab are effective options for amRCC after VEGF-targeted treatment.
- Considerable uncertainty exists regarding the comparative effectiveness of these agents against each other and older treatments like axitinib and sorafenib.
- Further research is needed to clarify the optimal sequencing and comparative efficacy of these advanced therapies.
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