Originally published as JCO Early Release 10.1200/JCO.2008.21.7034 on August 3 2009

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Phase II Study of Axitinib in Sorafenib-Refractory Metastatic Renal Cell Carcinoma

From the Cleveland Clinic Taussig Cancer Institute, Cleveland, OH; University of Wisconsin Carbone Comprehensive Cancer Center, Madison, WI; Fox Chase Cancer Center, Philadelphia, PA; University of Chicago, Chicago, IL; Pfizer Oncology, La Jolla, CA; Pfizer Oncology, New London, CT; and New York Medical College, New York, NY.

Corresponding author: Brian I. Rini, MD, Department of Solid Tumor Oncology and Urology, Cleveland Clinic Taussig Cancer Institute, 9500 Euclid Ave, Desk R35, Cleveland, OH, 44195; e-mail: rinib2{at}ccf.org.

Purpose To investigate the efficacy and safety of axitinib, an oral, potent, and selective inhibitor of vascular endothelial growth factor (VEGF) receptors 1, 2, and 3 in patients with metastatic renal cell carcinoma (mRCC) refractory to prior therapies that included, but were not limited to, sorafenib.

Patients and Methods In this multicenter, open-label, phase II study, patients with sorafenib-refractory mRCC received a starting dose of axitinib 5 mg orally twice daily. A one-arm, single-stage design was used to estimate the primary end point of objective response rate (ORR), defined by RECIST (Response Evaluation Criteria in Solid Tumors). Secondary end points included safety, duration of response, progression-free survival (PFS), overall survival (OS), and patient-reported outcomes.

Results Of 62 patients recruited, 100% had received prior sorafenib, and 74.2% had received two or more prior systemic treatments. The axitinib dose was titrated to greater than 5 mg twice daily in 53.2% of patients, and 35.5% of patients had the dose modified to less than 5 mg twice daily. In 62 patients evaluable for response, the ORR was 22.6%, and the median duration of response was 17.5 months. Median PFS and OS times were 7.4 months (95% CI, 6.7 to 11.0 months) and 13.6 months (95% CI, 8.4 to 18.8 months), respectively. All-causality grade 3 to 4 adverse events included hand-foot syndrome (16.1%), fatigue (16.1%), hypertension (16.1%), dyspnea (14.5%), diarrhea (14.5%), dehydration (8.1%), and hypotension (6.5%).

Conclusion Axitinib has antitumor activity in patients with mRCC refractory to prior VEGF-targeted therapy, including sorafenib. Toxicities were mild to moderate and were manageable. A randomized, phase III trial to compare axitinib with sorafenib in patients who have mRCC refractory to one prior first-line therapy regimen is underway.

Supported by Pfizer Oncology.

Presented in part at the 43rd Annual Meeting of the American Society of Clinical Oncology, June 1-5, 2007, Chicago, IL; the 14th Annual European Cancer Conference, September 23-27, 2007, Barcelona, Spain; the 44th Annual Meeting of the American Society of Clinical Oncology, May 30-June 3, 2008, Chicago, IL; the 7th International Kidney Cancer Symposium, September 26-27, 2008, Chicago, IL; and the 33rd European Society for Medical Oncology Congress, September 12-16, 2008, Stockholm, Sweden.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Clinical Trials repository link available on JCO.org.

Clinical trial information can be found for the following: NCT00282048 [ClinicalTrials.gov] .

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