Battling the Odds in RCC: Interview With Brian Rini, MD
Published Online: Saturday, May 5, 2012
Photo by © ASCO/Todd Buchanan 2012Brian Rini, MD
Ask Brian Rini, MD, and he’ll tell you his contributions to the battle against kidney cancer amount to a series of small victories in a war whose end is nowhere in sight.
As a clinical investigator, Rini said, “You learn to be humble, because most of what you do will not be successful. And, in the scheme of things, the advancements you help push forward will be relatively small.”
Despite that big-picture perspective, it’s hard for Rini—a renowned genitourinary specialist who holds posts at the Cleveland Clinic and Case Western Reserve University—to resist being excited about his latest achievement. As principal investigator on a global phase III trial of Pfizer’s axitinib (Inlyta) for patients with previously treated advanced renal cell carcinoma (RCC), Rini played a big part in moving the drug toward its approval January 27 by the FDA.
Rini’s AXIS trial demonstrated that axitinib significantly extended progression-free survival to a median of 6.7 months, compared with 4.7 months for those treated with sorafenib (Nexavar), a current standard of care for this patient population. That represents a 43% improvement.
A kinase inhibitor, axitinib is an oral therapy designed to selectively inhibit vascular endothelial growth factor receptor (VEGFR) 1, 2, and 3, which can influence tumor growth, vascular angiogenesis, and progression of cancer. The trial demonstrated that a VEGFRtargeted therapy can be effective following prior treatment options, including another VEGFR-targeted agent. It was the first trial ever to compare two kidney cancer drugs.
“I started working with this drug eight years ago, so it’s been a long road,” Rini said. “Thousands, if not tens of thousands, of people must come together to make trials like this happen, not to mention the patients. This is the fun part, when we get to the end and get results like this. It’s gratifying for all the hard work people have put in along the way.”
Research Focuses on AngiogenesisOver the past decade, the 42-year-old, whose research has focused on RCC, prostate, and other genitourinary cancers, as well as on antiangiogenic therapy and immunotherapy, has been involved in the development of several paradigmchanging treatments for kidney cancer. All of those, he said, have fallen within the general category of antiangiogenics, which prevent the generation of blood vessels needed for cancers to grow.
Among his proudest achievements was his leadership of a phase III trial of bevacizumab (Avastin) plus standard-of-care interferon-alfa that resulted in the combination’s 2009 approval by the FDA for use in metastatic RCC. Rini was also involved in a number of phase II trials that helped promising antiangiogenic drugs move toward approval.
Due to his efforts and the work of many others, Rini said, that in 2005 “we suddenly went from almost no therapies to many promising therapies. Now, patients with metastatic disease are living over twice as long as they did before, on average two years, not from any one drug, but from the whole list of drugs. It’s harder to measure quality of life and how much better they feel, but they feel better being alive than not, and that’s the ultimate test.”
While Rini recognizes that those accomplishments represent “a lot” of progress, he says they amount to “not much at the same time.” Moving forward, he’s determined to “continue to find new ideas and new drugs, and to develop them in unique ways.”
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