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Garcia JA , Hudes GR , Choueiri TK , Stadler WM , Wood LS , Gurtler J , Bhatia S , Joshi A , Hozak RR , Xu Y , Schwartz JD , Thompson JA
A phase 2, single-arm study of ramucirumab in patients with metastatic renal cell carcinoma with disease progression on or intolerance to tyrosine kinase inhibitor therapy
Cancer. 2014 Jun 1;120(11) :1647-55
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Abstract
BACKGROUND: Multitargeted tyrosine kinase inhibitors (TKIs) have antitumor activity in metastatic renal cell carcinoma (mRCC). Resistance to these agents develops frequently, and their use is often limited by intolerance. Ramucirumab is a recombinant human monoclonal antibody directed against human vascular endothelial growth factor receptor-2. For this study, the authors investigated the clinical efficacy and safety of ramucirumab in patients with TKI-resistant/intolerant mRCC. METHODS: In this single-arm phase 2 trial, patients received ramucirumab 8 mg/kg every 2 weeks until they developed disease progression or intolerable toxicity. The primary endpoint was the best objective response rate (ORR); additional endpoints included the disease control rate (DCR), progression-free survival (PFS), the median duration of overall response, and safety. RESULTS: Thirty-nine patients with RCC received ramucirumab monotherapy. Prior TKI therapy included sunitinib (59% of patients), sunitinib and sorafenib (30.8% of patients), and sorafenib (10.3% of patients). The ORR was 5.1% (95% confidence interval [CI], 0.6%-17.3%). The 12-week DCR was 64.1% (95% CI, 47.2%-78.8%). The median PFS was 7.1 months (95% CI, 4.1-9.7 months), and the median overall survival was 24.8 months (95% CI, 18.9-32.6 months). Grade 3 or higher adverse events that occurred in >/=5% of patients included grade 3 hypertension (7.7%) and proteinuria (5.1%). There was 1 on-study death from multiorgan failure. CONCLUSIONS: Although the study did not meet its primary endpoint of >/=15% ORR, ramucirumab was associated with evidence of antitumor activity in patients with TKI-resistant/intolerant mRCC. Ramucirumab was safe and well tolerated.
Notes
Garcia, Jorge A Hudes, Gary R Choueiri, Toni K Stadler, Walter M Wood, Laura S Gurtler, Jayne Bhatia, Shailender Joshi, Adarsh Hozak, Rebecca R Xu, Yihuan Schwartz, Jonathan D Thompson, John A eng Clinical Trial, Phase II Research Support, Non-U.S. Gov't Cancer. 2014 Jun 1;120(11):1647-55. doi: 10.1002/cncr.28634. Epub 2014 Feb 27.