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First-line antiangiogenics for metastatic renal cell carcinoma: A systematic review and network meta-analysis
Benoît Rousseau1, Emmanuelle Kempf2, Gaelle Desamericq3
1Department of Medical Oncology, Henri Mondor Hospital, Assistance Publique-Hôpitaux de Paris, Créteil, France; University of Paris-Est, Faculty of Medicine, Créteil, France; INSERM, U955, Team 18, Créteil, France.
Background:
Sunitinib, pazopanib, sorafenib, axitinib and bevacizumab are the five recommended antiangiogenic agents in first-line therapy for metastatic renal cell carcinoma (mRCC). Because these drugs underwent simultaneous clinical development, no direct efficacy and safety comparison was ever conducted, thus preventing optimal therapy choices.
Methods:
We performed a traditional and network meta-analysis to evaluate the efficacy and safety of mRCC-recommended first-line antiangiogenic agents. After a systematic review of Medline and Embase up to July 2014, we identified randomized clinical trials (RCTs) evaluating the outcomes of mRCC patients treated with sunitinib, pazopanib, sorafenib, axitinib and bevacizumab as first-line treatment. Endpoints of interest were response rate, progression-free survival (PFS), overall survival (OS), and safety.
Results:
We screened 769 abstracts and included nine RCTs with a total of 4282 patients. In the weighted pooled analysis, first-line antiangiogenic agents showed significant improvement in PFS (HR=0.6; 95% IC, 0.51-0.72) and OS (HR=0.85; 95% IC, 0.78-0.93) compared to control (placebo or interferon-alpha2a (INF)). Network meta-analysis showed no significant differences among antiangiogenic drugs in 6-month PFS, 1-year OS, disease control rate and drug-related safety for all-grade hypertension, diarrhea, weight-loss, nausea or anorexia. However, pazopanib showed a lower incidence of fatigue, anemia and hand foot skin reaction.
Conclusions:
This meta-analysis confirms the benefits of first-line antiangiogenic therapy in mRCC, with an improvement in OS. Sunitinib, pazopanib, axitinib and bevacizumab + INF offer similar efficacy but different safety profiles which can help clinicians to better personalize treatment decisions in patients with mRCC.
Insights
First-line antiangiogenic therapy significantly improves progression-free survival and overall survival in metastatic renal cell carcinoma (mRCC). While efficacy is similar across agents, pazopanib offers a better safety profile, aiding personalized mRCC treatment decisions.
Area of Science:
- Oncology
- Pharmacology
- Clinical Trials
Background:
- Five antiangiogenic agents (sunitinib, pazopanib, sorafenib, axitinib, bevacizumab) are recommended for first-line metastatic renal cell carcinoma (mRCC) therapy.
- Simultaneous clinical development prevented direct comparisons, hindering optimal treatment choices.
Purpose of the Study:
- To evaluate and compare the efficacy and safety of first-line antiangiogenic agents for mRCC.
- To provide data for personalized treatment decisions in mRCC patients.
Main Methods:
- Conducted a systematic review and meta-analysis of randomized clinical trials (RCTs) up to July 2014.
- Included nine RCTs with 4282 mRCC patients treated with sunitinib, pazopanib, sorafenib, axitinib, or bevacizumab.
- Evaluated endpoints including response rate, progression-free survival (PFS), overall survival (OS), and safety profiles.
Main Results:
- First-line antiangiogenic agents significantly improved PFS and OS compared to control.
- Network meta-analysis revealed no significant differences in efficacy (PFS, OS, response rate) or safety (hypertension, diarrhea, weight loss, nausea, anorexia) among the agents.
- Pazopanib demonstrated a lower incidence of fatigue, anemia, and hand-foot skin reaction.
Conclusions:
- First-line antiangiogenic therapy is beneficial for mRCC, improving overall survival.
- Sunitinib, pazopanib, axitinib, and bevacizumab + INF show similar efficacy but distinct safety profiles.
- These safety differences can guide clinicians in personalizing mRCC treatment.
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