Drugs in Clinical Development for Renal Cancer Summary and Table
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Drugs in Clinical Development for Renal Cancer Summary and Table
Ó Springer International Publishing Switzerland 2014
Treatment of metastatic renal cell carcinoma (RCC) is extremely challenging and, despite advances, patients with advanced renal cancer have a poor prognosis, with 5-year survival rates of \20 %. Current therapeutic options— surgery and, for metastatic disease, immunotherapy and, more recently, targeted anti-angiogenic therapy—are not curative and aim to slow the cancer growth rate and shrink existing tumours. Recent advances have led to identification of many targets and subsequent launch of targeted therapies, resulting in improved survival. Small molecule protein kinase inhibitors approved for advanced RCC include multiple kinase inhibitors sunitinib malate, sorafenib tosylate, pazopanib, axtinib, and mammalian target of rapamycin (mTOR) kinase inhibitors temsirolimus and everolimus (with axtinib, everolimus and sorafenib usually used second-line). In addition, bevacizumab, the first vascular endothelial growth factor (VEGF) monoclonal antibody (MAb), is approved for first-line treatment of advanced RCC in combination with interferon. Options for patients failing kinase inhibitor therapy are limited. Ongoing studies are investigating combination therapies, but current standard of care involves the sequential use of single agents. The drug development pipeline consists of many additional targeted therapies, to both proven and novel targets (see Table 1). Of these, angiogenesis inhibitors make up the largest group and include small molecules and monoclonal antibodies (MAbs) targeting specific growth pathways, such as VEGF, platelet-derived growth factor (PDGF), mTOR and a range of other kinases. Small molecules in phase III development include oral multitargeted receptor tyrosine kinase inhibitors cabozantinib
and dovitinib for second-line or greater treatment of metastatic RCC. Some marketed agents are being investigated in other indications. For example, sunitinib is phase III development as adjuvant treatment in patients at high risk of recurrent RCC, and phase II as neoadjuvant therapy in patients with high risk RCC undergoing nephrectomy. Sorafenib is in phase III development as adjuvant therapy and as first- or second-line therapy in patients with advanced or metastatic RCC. Following the success of bevacizumab, several other MAbs are in phase III development including IV naptumomab estafenatox, a T cell stimulant in development for late-stage renal cancer as combination therapy, and nivolumab, a fully human IgG4 monoclonal antibody targeting the programmed cell death-1 receptor (PCD1R) in development for late-stage metastatic renal cancer as second-line therapy or greater. Another area of intense research for treatment of renal cancer is vaccine therapy. Vaccine technology uses autologous tumour cells or products extracted from tumour cells to target the tumour. Recently the intradermal (ID) agent RenialeÒ was approved in Europe as adjuvant therapy for RCC and is expect
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