Authors' objectives:

This assessment summarizes and evaluates evidence on outcomes of bevacizumab for clear cell renal carcinoma and other malignancies besides colorectal cancers. For each cancer, evidence on bevacizumab is assessed separately as second- or subsequent-line therapy for advanced or metastatic disease, as first-line therapy for advanced or metastatic disease, or as adjuvant therapy for early stage disease. Another Assessment (Vol. 21, No. 8) summarizes and evaluates evidence on health outcomes of bevacizumab for breast cancer and non-small cell lung cancer.

Authors' results and conclusions: The literature search identified one 3-arm RCT on second-line therapy, and one single-arm study without controls on a mixed patient group receiving first- or second-line therapy. The RCT enrolled patients with metastatic disease who were ineligible for (5;8%) or failed (92;95%) interleukin-2 (IL-2). They were randomized to placebo or to 3 mg/kg or 10 mg/kg bevacizumab. The median progression-free interval was significantly longer in each arm given bevacizumab than for controls (n=40; 2.5 months), with a larger increase in the high-dose (n=39; 4.8 months; p<0.001) than the low-dose arm (n=37; 3.0 months; p=0.041). Effects of bevacizumab on OS were not statistically significant, but 22 of 40 controls crossed over to bevacizumab when they progressed. An independent data safety and monitoring board stopped accrual when the second interim analysis showed that the higher-dose bevacizumab arm crossed the prespecified O'Brien-Fleming boundary (p=0.015 in the trial's second year) for time to progression, a primary trial outcome. The literature search found no evidence directly comparing effects of bevacizumab with those of either multi-targeted protein kinase inhibitor (sorafenib or sunitinib) recently approved to treat renal cell carcinoma. The search also found no evidence on outcomes of bevacizumab in patients who progressed after interferon alfa, sorafenib, or sunitinib. Trials are in progress on some of these comparisons and patient groups.

Authors' recommendations: An RCT showed that, compared with no second-line therapy, bevacizumab improved PFS of patients progressing after IL-2 therapy (92;95% of those randomized). However, the trial did not detect an effect of bevacizumab on OS. When this RCT was published, no alternative treatments with proven effectiveness were available for these patients. Subsequently, the U.S. Food and Drug Administration approved two new drugs for renal carcinoma, sorafenib and sunitinib. A large phase III RCT for the same indication showed that sorafenib improved OS compared with placebo. Presently, it is not possible to determine whether outcomes of bevacizumab are at least equivalent to those of sorafenib. Nor is there evidence on the outcomes of bevacizumab for patients who progress after interferon alfa, sorafenib or sunitinib. Thus, no conclusions are possible on outcomes of bevacizumab for patients with metastatic clear cell renal carcinoma that progressed after treatment with IL-2, interferon alfa, sorafenib, or sunitinib.

Authors' methods: Review

Project Status: Completed

URL for project: http://www.bcbs.com/blueresources/tec/contact-tec.html

Year Published: 2006

URL for published report: BlueCross BlueShield Association

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: United States

Organisation Name: BlueCross BlueShield Association

Contact Address: BlueCross BlueShield Association, Technology Evaluation Center, 225 North Michigan Ave, Chicago, Illinois, USA. Tel: 888 832 4321

Contact Name: tec@bcbsa.com

Contact Email: tec@bcbsa.com

Copyright: <p>BlueCross BlueShield Association (BCBS)</p>