Novartis’ RAD001 Doubles Progression-Free Survival in Advanced Renal Cancer Trial
This article was originally published in The Pink Sheet Daily
Executive Summary
Median PFS was 4 months with everolimus, versus 1.9 months with placebo.
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Novartis' experimental drug RAD001 (everolimus) doubled progression-free survival of patients with metastatic kidney cancer in a placebo-controlled Phase III trial, the firm reported May 31 at the American Society of Clinical Oncology annual meeting. The data were not scheduled to be released until the meeting, but ASCO lifted an embargo on Friday, May 16, after a news report appeared. Until then the abstract had not been among the thousands posted on the society's Web site (www.asco.org) in advance of the meeting, held May 30 to June 2 in Chicago. Only 37 percent of patients on RAD001 had progressed, as compared with 65 percent of the placebo group, according to the late-breaking abstract. Median progression-free survival was 4 months with RAD001 vs. 1.9 months with placebo (hazard ratio .30, P less than .0001). All 410 patients in the trial already had failed treatment with sunitinib (Pfizer's Sutent ) and/or sorafenib (Bayer/Onx' Nexavar ), two targeted agents recently approved for advanced kidney cancer. Prior treatment with bevacizumab (Genentech's Avastin ) and interferon also was allowed. Novartis announced in February that the company-sponsored international trial had been halted because the study met its primary endpoint of significantly better progression-free survival by independent review using Response Evaluation Criteria in Solid Tumors criteria (1 (Also see "Good Results Stop Novartis’ Phase III Everolimus Trial" - Pink Sheet, 28 Feb, 2008.)). The firm plans to file RAD001 for advanced kidney cancer later this year. From September 2006 to October 2007 investigators in 12 countries randomized 272 patients to RAD001 and 138 to placebo. The arms were described as well-balanced, with a pooled median age of 60 years and similar proportions that had received prior therapies targeting vascular endothelial growth factor receptors: sunitinib (71 percent of patients), sorafenib (55 percent), and sunitinib and sorafenib (26 percent). The abstract reports that 191 (47 percent) of 410 patients had progressed. The greatest benefit was observed in patients stratified as having favorable prognoses by Memorial Sloan-Kettering Cancer Center criteria, but all three risk groups did significantly better with RAD001. Median progression-free survival was 5.5 months vs. 2.2 months in 118 patients with favorable risk, 3.9 months vs. 1.8 months in 231 patients with intermediate risk, and 3.6 months vs. 1.9 months in 61 patients with poor risk. Adverse events caused 10 percent of patients on RAD001 to stop the drug and 4 percent to reduce the dose. The most common toxicities were stomatitis, anemia, and asthenia. Overall survival, the secondary endpoint, still is being assessed, with 68 deaths noted in the abstract. "RAD001 resulted in a statistically and clinically significant improvement in PFS over placebo with a favorable safety profile in patients with mRCC [metastatic renal cell cancer] after progression on other targeted therapies," Robert J. Motzer, Memorial Sloan-Kettering Cancer Center, et al. concluded. -Jane Salodof MacNeil [Editor's note: This story appears courtesy of Elsevier Global Medical News. For more information, please contact Michael Magoulias at 240-221-4530.] |