Risk of primary progressive disease with tyrosine kinase inhibitors sorafenib and sunitinib in patients with renal cell carcinoma: A meta-analysis.

Abstract

4616 Background: Tyrosine kinase inhibitors (TKIs) sorafenib and sunitinib are used extensively in the treatment of advanced renal cell carcinoma (RCC). Treatment failure due to drug resistance can occur as primary or secondary progressive disease. To better understand the drug resistance, we performed a systemic review and meta-analysis of published clinical studies to determine the risk of primary progressive disease (PPD) with sorafenib and sunitinib in RCC patients. Methods: We searched databases from Pubmed, Web of Science, and abstracts presented at the American Society of Clinical Oncology conferences up to August, 2009 to identify relevant studies. PPD was defined as progressive disease as best response by RECIST criteria. Eligible studies include case series and clinical trials in which RCC patients were treated with sorafenib or sunitinib as a single agent. Incidence, relative risk (RR), and 95% confidence intervals (CIs) were calculated using a random-effects or fixed-effects model. Results: A total of 7,588 patients from 30 studies were included for analysis. The overall incidence of PPD with TKIs was 22.4% (95% CI: 18.7-26.6%), with 22.6% and 22.4% for sorafenib and sunitinib, respectively. There was no significant difference in the risk of developing PPD with TKI between non-clear-cell and clear-cell RCC (RR 1.09, p=0.086). Notably, prior cytokine therapy increased the risk of PPD with sunitinib (RR, 1.18, 95% CI: 1.05-1.34; p=0.007), but not sorafenib (RR, 0.97, 95% CI, 0.78-1.19; p=0.75), in comparison with no prior treatment. Furthermore, prior treatment with sorafenib did not significantly increase the risk of PPD with subsequent sunitinib in comparison with no prior treatment (RR 1.33, 95% CI: 0.98-1.80; p=0.069); however, prior treatment with sunitinib significantly increased the risk of PPD with subsequent sorafenib (RR 3.53, 95% CI: 2.88-4.34; p<0.0001). Conclusions: Early treatment failure from PPD in advanced RCC patients may vary with prior cytokine or TKI therapies. Sorafenib and sunitinib may have different mechanisms in the development of drug resistance. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Onyx, Wyeth