A large, randomized, head-to-head trial comparing pazopanib (Votrient) to sunitinib (Sutent) shows treatment-naive metastatic renal cell carcinoma (RCC) patients respond as well to both oral therapies. The COMPARZ trial showed a median progression-free survival of 8.4 months for the pazopanib arm compared to 9.5 months for the sunitinib arm—the difference was not statistically significant. The hazard ratio (HR), 1.047, suggests a near identical progression-free survival result with both drugs.
Chemical structure of pazopanibThe overall response rate was also not statistically significant—31% for patients taking pazopanib compared to 25% of patients taking sunitinib (P = .03). Median overall survival was 28.4 months in the pazopanib arm compared to 29.3 months in the sunitinib arm (HR = 0.91). Robert Motzer, MD, of Memorial Sloan-Kettering Cancer Center in New York presented the data at the European Society for Medical Oncology (ESMO) 2012 Congress in Vienna.
Pazopanib was approved by the US Food and Drug Administration (FDA) for the treatment of metastatic RCC in 2009. Sunitinib (Sutent) was approved for metastatic RCC back in 2006 as an accelerated approval—the drug received a full approval status in 2007 after demonstrating an improved progression-free survival benefit. Both drugs are multiple receptor tyrosine kinase inhibitors whose targets include platelet-derived growth factor receptors (PDGF-Rs) and vascular endothelial growth factor receptors (VEGFRs). Sunitinib has been traditionally considered as a reference standard of care for metastatic RCC.
The COMPARZ trial randomized a total of 1,110 patients to either 800 mg pazopanib, given once daily, or 50 mg of once daily sunitinib given in 6-week cycles (4 weeks of treatment followed by a 2 week off period). The primary endpoint was progression-free survival—the trial was powered to establish noninferiority.
Besides a direct comparison of efficacy, the trial aimed to assess any differences in safety and tolerability of the two oral tyrosine-kinase inhibitor therapies. Based on patient quality-of-life questionnaires, pazopanib was favored by patients over sunitinib due to improved tolerability. Patient questionnaires showed a better life quality in 11 of 14 categories, assessed after 6 months of therapy.
Side effects such as skin sores, fatigue, and thrombocytopenia occurred at a lower frequency among patients who took pazopanib. Fatigue was reported by 55% of patients taking pazopanib compared to 63% of patients taking sunitinib. Pazopanib was also associated with a lower frequency of taste alteration—26% of pazopanib patients reported altered taste compared to 36% of sunitinib patients. Pazopanib was associated with higher liver enzyme levels compared to sunitinib, 31% vs18%, respectively (P < .05).
“These results are not surprising as the two drugs have similar biological mechanisms and historically have shown comparable clinical benefit,” said Roberto Pili, MD, coleader of the genitourinary program at Roswell Park Cancer Institute in Buffalo, New York, who was not involved in the study. Dr. Pili emphasized that the quality of life assessment, as mentioned during the presentation at ESMO, may have been biased in favor of pazopanib as the worst symptoms are experienced at the end of the sunitinib cycle, when patients fill out the quality-of-life questionnaires.
Will these results change treatment of RCC? “It is hard to predict whether these new data will change practice patterns, but it is reasonable to expect that more physicians will start to prescribe pazopanib based also on the results from the PISCES study where the majority of patients preferred pazopanib vs sunitinib in terms of side effects following a short treatment period,” said Dr. Pili.
There have been many new agents in development for metastatic RCC patients over the last few years. New second-generation tyrosine kinase inhibitors such as axitinib (Inlyta), which is currently approved as a second-line therapy, has shown clinical benefit as a first-line therapy in patients as well. Tivozanib is another tyrosine kinase inhibitor also in development for first-line RCC patients.
“The second generation of tyrosine kinase inhibitors appears to be more tolerable and equally effective if not more as compared with the first tyrosine kinase inhibitors approved,” said Dr. Pili. “These new agents will likely become the new standard of care for newly diagnosed metastatic RCC.” Dr. Pili pointed out agents with other mechanisms of action that are on the horizon include the immunotherapy antibody BMS-936558, which has shown promising phase I data in metastatic RCC patients.
