Targeted Therapy for metastatic Renal Cell Carcinoma: A Review of the Recent AXIS Clinical Trial
Department of Solid Tumor Oncology
Cleveland Clinic Taussig Cancer Institute
Glickman Urological Institute
Kidney cancer has seen the introduction of several agents which target blood vessels in recent years. These anti-angiogenic agents have demonstrated clear anti-tumor activity and have become the standard of care. The trials that led to FDA-approval of these agents compared them to inactive compounds such as interferon or placebo. What is needed at present are clinical trials comparing active agents to each other to get a better sense of risk and benefit of each approach for individual patients.
The AXIS trial was a global phase III trial that randomized metastatic kidney cancer patients to either axitinib, a potent inhibitor of the VEGF receptor, or sorafenib, an FDA approved inhibitor of the VEGF receptor. These patients had disease progression despite one prior systemic therapy regimen (one of several which were approved at the time of trial design – sunitinib, cytokines, bevacizumab or temsirolimus). The hypothesis was that more biochemically potent VEGFR inhibition with axitinib would translate into clinical benefit for patients, as measure by progression-free survival.
The results showed that the risk of progression on axitinib was reduced by 33% compared to sorafenib, corresponding to a 2-month median PFS advantage. These data are the first to compare active drugs in kidney cancer, and provide data to help clinicians make treatment decisions for patients. For instance, the tolerability of each drug was comparable, but the specific side effects were different. Axitinib-treated patients experienced more hypertension, hoarseness and hypothyroidism, while sorafenib-treated patients experience more rash, hand-foot syndrome and alopecia.
Additional work is clearly needed to predict the risk and benefit for an individual patient. Intensive efforts are underway to analyze blood and tissue from this and other trials to develop a predictive biomarker for VEGF-targeting agents in kidney cancer. In the meantime, head-to-head clinical trials such as AXIS and other ongoing trials to be reported in the next year, will provide information on the comparative risk and benefit of targeted therapy approaches in metastatic kidney cancer.
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