Matthew R. Cooperberg, MD, MPH
This year’s approval of radium-223 chloride (Xofigo) continues the 4-year run of important new prostate cancer drugs, and Matthew Cooperberg, MD, MPH, thinks the run will continue over the next few years.
“Between 2004 and 2010, we didn’t see any new drugs for prostate cancers. Since then, we’ve had six approved, with more in late-stage development, and most of them have non-overlapping mechanisms of action,” said Cooperberg, a urologic oncologist and epidemiologist specializing in prostate cancer at the UCSF Cancer Center.
“We’re right in the middle of a complete paradigm shift. We’re getting new information nearly every month about efforts to combine products, and we’ll soon be struggling with questions about how to afford all these powerful new medications.”
Radium-223 represents a breakthrough, Cooperberg believes, both because it provides several extra months of life to men with castration-resistant prostate cancer (CRPC) and bone metastases, and because it marks the arrival to prostate cancer treatment of a new type of radiation—alpha radiation—that should prove particularly effective for targeting cancer cells in the bones.
Cooperberg sees similar breakthrough potential in the first-in-class androgen-receptor inhibitor enzalutamide (Xtandi). The drug, which was first approved in 2012 as a postchemotherapy treatment for CRPC, took a major step toward prechemotherapy approval this year, when a phase III trial was stopped for benefit.
“In addition to the clinical benefits enzalutamide and abiraterone acetate [Zytiga] provide for patients— remarkable benefits for some—the development and success of these drugs have taught us how little we understood about castration-resistant cancer,” Cooperberg said. “Their effectiveness has demonstrated that, contrary to previous belief, androgens do continue to drive growth and progression of CRPC, even after we eliminate the body’s ability to produce androgens.”
Cooperberg believes the upcoming year may provide some initial guidance to clinicians who wonder how to use enzalutamide and radium-233 with other medications for CRPC—medications like abiraterone, which moved from experimental compound to second-line therapy to first-line therapy in just 20 months.
Should they be used individually or paired? Should the pair be further combined with docetaxel? If they work better individually, which patients should get which drug first? Does the failure of one indicate that none will work on a given patient?
Add radium-233, together with sipuleucel-T (Provenge), cabazitaxel (Jevtana), and denosumab (Xgeva) into the mix and the possible combinations and sequences become highly complex.
Randomized trials are unlikely to determine the perfect sequence of individual medications, but trials will likely test the effectiveness of combinations, and Cooperberg sees reason to hope that the drugs—with their varying mechanisms of action—may combine to give years of extra life to patients.
“The last question, of course, will be how to afford a combination treatment,” Cooperberg said. “All of these drugs are extremely expensive and, because they’re so new, most are patent protected for years to come. The cost is a real worry, but it’s a much better worry than a lack of treatments, which was the biggest concern until recently.”
Matthew Cooperberg, MD, MPH, is an assistant professor of Urology; Epidemiology & Biostatistics, at the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center.