Open Access Highly Accessed Research article

Comparative effectiveness of approved first-line anti-angiogenic and molecularly targeted therapeutic agents in the treatment of good and intermediate risk metastatic clear cell renal cell carcinoma

Benjamin Haaland12*, Akhil Chopra3, Sanchalika Acharyya1, André P Fay45 and Gilberto de Lima Lopes678

Author Affiliations

1 Centre for Quantitative Medicine, Office of Clinical Sciences, Duke-National University of Singapore Graduate Medical School, 8 College Road, Singapore 169857, Singapore

2 Department of Statistics and Applied Probability, National University of Singapore, Science Drive 2, Singapore 117546, Singapore

3 Johns Hopkins Singapore International Medical Center, Jalan Tan Tock Seng, Singapore 308433, Singapore

4 Post-Graduate Program - School of Medicine, Pontificia Universidade Catolica do Rio Grande do Sul, Av. Ipiranga, 6681 - Partenon, Porto Alegre RS 90619-900, Brazil

5 Dana-Farber Cancer Institute, Lank Center for Genitourinary Oncology, 450 Brookline Ave, Boston MA 02215-5450, USA

6 Oncoclinicas do Brasil, Avenida Barbacena 472-14° andar, Belo Horizonte, MG, Brazil

7 Hospital do Coração Cancer Center (HCor Onco), São Paulo, Brazil

8 Johns Hopkins University, Baltimore, MD, USA

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BMC Cancer 2014, 14:592  doi:10.1186/1471-2407-14-592

Published: 15 August 2014



Based on improved clinical outcomes in randomized controlled clinical trials (RCTs) the FDA and EMA have approved bevacizumab with interferon, sunitinib, and pazopanib in the first-line treatment of low to intermediate risk metastatic clear cell renal cell carcinoma (mRCC). However, there is little comparative data to help in choosing the most effective drug among these agents.


We performed an indirect comparative effectiveness analysis of the pivotal RCTs of bevacizumab with interferon, sunitinib, or pazopanib compared to one another or interferon alone in first-line treatment of metastatic or advanced RCC. Endpoints of interest were overall survival (OS), progression free survival (PFS), and response rate (RR). Adverse events were also examined.


The meta-estimate of the hazard ratio (95% confidence interval) for OS for bevacizumab with interferon vs. interferon alone was 0.86 (0.76-0.97), for sunitinib vs. interferon alone was 0.82 (0.67-1.00), for pazopanib vs. interferon alone was 0.74 (0.57-0.97), for sunitinib vs. bevacizumab with interferon was 0.95 (0.75-1.20), for pazopanib vs. bevacizumab with interferon was 0.86 (0.64-1.16), and for pazopanib vs. sunitinib was 0.91 (0.76-1.08). Similarly, bevacizumab with interferon, sunitinib, or pazopanib had better PFS and RR than interferon alone. Sunitinib and pazopanib had better RR than bevacizumab with interferon and there was suggestive evidence pazopanib may outperform sunitinib in terms of RR.


Bevacizumab with interferon, sunitinib, and pazopanib are adequate first-line options in treatment of mRCC. Interferon alone should not be considered an optimal first-line treatment.

Renal cell carcinoma; VEGF-targeted therapy; Bevacizumab; Sunitinib; Pazopanib; Interferon