Pazopanib or Sunitinib in Metastatic Renal Cancer

FigureSAN FRANCISCO—When faced with a decision as to whether to treat metastatic renal cell carcinoma with pazopanib or sunitinib, the answer is: Yes (Abstract 544). In a study presented at the 2016 Genitourinary Cancers Symposium, researchers found little differences in efficacy with the two agents among these kidney cancer patients. “These two drugs could be used interchangeably as first line therapy in metastatic renal cell carcinoma,” Jose Ruiz-Morales, MD, a fellow in Genitourinary Cancer at the Tom Baker Cancer Center at the University of Calgary, Alberta, Canada, told OT at his poster presentation. And in second-line therapy, it again made no difference in outcomes which drug was used first or second, he said. “The choice for which drug to use may come down to price, toxicity, prior use, and things like that,” Ruiz-Morales said, noting that sunitinib, although the older of the two drugs, is more expensive than pazopanib. Study Details In his study, which included 3,606 patients with metastatic renal cell carcinoma treated with first line sunitinib (3,226 patients) and the 380 patients treated with pazopanib, the progression-free survival and overall survival showed overlapping event curves. The median progression-free survival with sunitinib was 7.22 months compared with median progression-free survival of 6.83 months with pazopanib (P=0.33), a non-significant difference. The median overall survival of these patients was 20.1 months among the patients who were taking sunitinib compared with 23.68 months among the patients on pazopanib (P=0.19), also non-significant. When Ruiz-Morales and his colleagues scrutinized outcomes in the second-line setting, they again were unable to distinguish a significant difference between treatment arms. Patients receiving sunitinib in the second-line setting achieved a median of 3.67 months of progression-free survival compared with 4.53 months median progression-free survival with pazopanib (P=0.47), a non-significant finding. As for median overall survival in the second-line setting, patients who were treated with sunitinib achieved 12.88 months compared with a median overall survival of 12.91 months with pazopanib (P=0.4). The comparisons all considered a variety of prognostic factors. Study Participants Patients selected in Ruiz-Morales' trial were generally in good performance status. About 23 percent of the sunitinib patients and 25 percent of the pazopanib patients had less than an 80 percent score on the Karnofsky scale. About 73 percent of the patients on sunitinib were men; approximately 74 percent of those on pazopanib were men, the researchers reported. Some 58 percent of the patients on sunitinib had been diagnosed with metastatic renal cell carcoinoma within a year of beginning treatment compared with 52 percent of the patients treated with pazopanib (P=0.0189), a statistically significant difference. About 76 percent of the sunitinib patients had undergone nephrectomy compared with 80 percent of the patients on pazopanib (P=0.0980), a non-significant difference. The patients treated with sunitinib appeared to have worse prognostic factors based on the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) criteria. Ruiz-Morales reported that 17.3 percent of the patients on sunitinib had favorable prognostic factors compared with 25 percent of those treated with pazopanib. He reported that 55.6 percent of the sunitinib patients were diagnosed with intermediate prognostic factors compared with 53 percent of the pazopanib patients. Poor prognostic factors were observed among 27.1 percent of the sunitinib patients compared with 22 percent of the pazopanib patients. The differences in prognostic factors—taken into consideration in survival calculations—was statistically significant (P=0.0027), the researchers reported. Response to Treatment Responses to treatment were similar, the researchers reported. Ruiz-Morales said 62 of the sunitinib patients achieved a complete response—about 2.3 percent of the patients in the study. He said four of the pazopanib patients (1.4%) were able to achieve a complete response. About 28 percent of the patients on sunitinib achieved an objective partial response, compared with 24.3 percent of the patients on pazopanib.FigureStable disease was achieved by 44.58 percent of the sunitinib patients and by 52.5 percent of those on pazopanib. About 25 percent of the patients on sunitinib progressed compared with 21.8 percent of the patients taking pazopanib, Ruiz-Morales said. The differences in response did not achieve statistical significance (P=0.0909). “We confirmed in a population-based setting that sunitinib and pazopanib have similar efficacy in the first-line treatment of metastatic renal cell carcinoma and the choice of one drug or the other does not affect outcomes with subsequent second-line therapy,” Ruiz-Morales said. He noted that the study was unable to capture individualization of dosing of sunitinib and that is a subject for future exploration. Validation of Results In commenting on the study, Xinhua Zhu, MD, attending physician in the Department of Genitourinary Medical Oncology, Northwell Health Cancer Center, Lake Success, New York, said that the new work in a “real world” setting further validated the results of the COMPARZ trial (http://www.ncbi.nlm.nih.gov/pubmed/23964934). “Clinically if the patients with metastatic clear cell renal cell carcinoma require first line tyrosine kinase inhibitors,” Zhu told OT, “I always select pazopanib as opposed to sunitinib, given pazopanib and sunitinib have similar clinical outcomes, but the safety and quality-of-life profiles favor pazopanib based on COMPARZ trial.” The COMPARZ trial was funded by GlaxoSmithKline Pharmaceuticals. The symposium is co-sponsored by the American Society of Clinical Oncology, the American Society for Radiation Oncology, and the Society of Urologic Oncology.

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