New Treatment Options for Advanced Renal Cell Carcinoma
The results from three phase III trials shed new light on treatment options for patients with advanced renal cell carcinoma. The studies were presented at the ESMO 2012 Congress of the European Society for Medical Oncology in Vienna.
More than 58,000 people are diagnosed with kidney cancer in the United States each year. The most common type of kidney cancer is renal cell carcinoma (RCC), which starts in the lining of very small tubes (tubules) in the kidney. For people with advanced RCC (cancer that has spread to other parts of the body), targeted therapies can play an important role in treatment.
The COMPARZ trial is a phase III randomized, open-label study comparing two targeted drugs, Votrient® (pazopanib) and Sutent® (sunitinib), for the first-line treatment of metastatic RCC. Both drugs are oral targeted agents that work by inhibiting multiple biologic pathways involved in cancer growth and spread. Sutent has been considered the standard treatment; however, some data has indicated that Votrient may be equally as effective with fewer side effects. This study aimed to provide a direct comparison of the efficacy, safety, and tolerability of the two drugs.
The study involved 1,100 patients with clear cell metastatic RCC who had not received previous treatment. Patients were randomly assigned to receive Votrient or Sutent. The primary endpoint of the study was to determine whether progression-free survival was equivalent between the two drugs. Secondary endpoints included safety and quality of life.
The results indicated that the two drugs were similarly effective—with a median progression-free survival of slightly more than 10 months for both. Although both drugs produced side effects, patients receiving Votrient experienced less fatigue and skin sores, both of which are side effects that can be quite troublesome and impact quality of life. Quality-of-life questionnaires favored Votrient over Sutent and suggested that Votrient may be more tolerable.
The results of this study are important because they show that Votrient is not inferior to Sutent and they provide a second option for first-line treatment of metastatic RCC.
The INTORSECT Trial
The INTORSECT trial was a multi-center, randomized, open-label phase III trial that compared the efficacy and safety of Torisel® (temsirolimus) with Nexavar® (sorafenib) in patients with metastatic RCC who failed prior therapy with Sutent.
Both drugs are targeted agents, but they inhibit different growth factors. Torisel targets mTOR (mammalian target of rapamycin kinase), which regulates cell growth and proliferation; whereas Nexavar inhibits several tyrosine kinases, including VEGF (vascular endothelial growth factor) receptors.
This is the first phase III trial directly comparing a VEGF inhibitor to an mTOR inhibitor in this setting—and the results will have important treatment implications for metastatic RCC.
The study included 511 patients with RCC whose disease had progressed after first-line treatment with Sutent and who had an ECOG performance status of 0 or 1. The results indicated that Torisel was not superior to Nexavar. Median progression-free survival with Torisel was 4.28 months compared to 3.91 months for Nexavar. Median overall survival was 12.27 months for Torisel compared to 16.64 months for Nexavar.
The researchers concluded that Torisel does not improve survival over Nexavar in the second-line setting and suggest that VEGF inhibitors may be a better option than mTOR inhibitors for patients whose disease progresses after treatment with Sutent.
The INTORACT Trial
The INTORACT trial was a phase IIIb, randomized, open-label multi-center study that compared Torisel plus Avastin® (bevacizumab) with interferon plus Avastin as first-line treatment in 791 patients with predominantly clear cell metastatic renal cell carcinoma.
Avastin is a targeted therapy that inhibits the VEGF pathway, whereas Torisel inhibits the mTOR pathway. Although early results had looked promising, final results indicated that Torisel plus Avastin offered no advantage over interferon plus Avastin.
Median progression-free survival was 9.1 months in the Torisel group compared to 9.3 months in the interferon group. Median overall survival was 25.8 months in the Torisel group and 25.5 months in the interferon group.
The researchers concluded that Torisel plus Avastin is not superior to interferon plus Avastin in the first-line treatment of patients with clear cell metastatic RCC.
 Motzer RJ, Hutson TE, Reeves J, et al. Randomized, open label, phase III trial of pazopanib versus sunitinib in first-line treatment of patients with metastatic renal cell carcinoma (mRCC); Results of the COMPARZ trial. Presented at the 37th Congress of the European Society for Medical Oncology (ESMO), Vienna, Austria, September 28-October 2, 2012. Abstract LBA8.
 Hutson T, Escudier B, Esteban E, et al. Temsirolimus vs Sorafenib as Second Line Therapy in Metastatic Renal Cell Carcinoma: Results From the INTORSECT Trial. Presented at the 37th Congress of the European Society for Medical Oncology (ESMO), Vienna, Austria, September 28-October 2, 2012. Abstract LBA22.
 Rini BI, Bellmunt J, Clancy J, et al. Randomized Phase IIIb Trial of Temsirolimus and Bevacizumab versus Interferon and Bevacizumab in Metastatic Renal Cell Carcinoma: Results from INTORACT. Presented at the 37th Congress of the European Society for Medical Oncology (ESMO), Vienna, Austria, September 28-October 2, 2012. Abstract LBA21.
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