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. Issue 11 (27th February 2014)

• Record Type: Journal Article
• Authors: 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.
• Is Part Of: Cancer. Volume 120:Issue 11(2014)
• Page Start: 1647
• Page End: 1655
• Publication Date: 2014-02-27
• Subjects: Cancer -- Periodicals; Cancer -- Cytopathology -- Periodicals; 616.99405
• DOI: 10.1002/cncr.28634
• Languages: English
• ISSNs: 0008-543X

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="cncr28634-sec-0001" sec-type="section"> <title>BACKGROUND</title> <p>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.</p> </sec> <sec id="cncr28634-sec-0002" sec-type="section"> <title>METHODS</title> <p>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.</p> </sec> <sec id="cncr28634-sec-0003" sec-type="section"> <title>RESULTS</title> <p>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.</p> </sec> <sec id="cncr28634-sec-0004" sec-type="section"> <title>CONCLUSIONS</title> <p>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. <bold><italic>Cancer</italic> 2014;120:1647–1655</bold>. © <italic>2014 American Cancer Society</italic>.</p> </sec> </abstract>