Nick Mulcahy

March 16, 2012

March 16, 2012 (Hollywood, Florida) — After 2 years of major changes to the prostate cancer guidelines from the National Comprehensive Cancer Network (NCCN), the organization's 2012 guidance is relatively unrevised.

The new recommendations are minor and not comparable in magnitude to the grand changes that occurred in either 2010, when active surveillance was introduced as the sole treatment option for many men with low- and very-low-risk disease, or 2011, when systemic therapy for metastatic disease was completely revamped.

However, the guidelines will be back in change mode soon — especially in the area of the treatment of castration-resistant metastatic disease, Sandy Srinivas, MD, from Stanford Comprehensive Cancer Institute in Palo Alto, California, announced here at the NCCN 17th Annual Conference.

Two new drugs — radium 223 (Alpharadin, Bayer) and MDV3100 (Medivation) — are "likely to be approved by the end of the year," she told meeting attendees. In addition, a drug already approved, abiraterone (Zytiga, Janssen), is likely to get another indication, she said.

None of these anticipated events has yet affected the NCCN guidelines.

Radium 223 is for patients with castration-resistant prostate cancer (CRPC) and bone metastases, and is now under review by the US Food and Drug Administration (FDA), said Dr. Srinivas. She reported that data on the drug were most recently presented at the 2012 Genitourinary Cancer Symposium.

As previously reported by Medscape Medical News, the pivotal trial on radium 223 was stopped early when an interim analysis found a significant improvement in survival. Patients treated with the drug had a significantly longer median survival than patients on placebo (14.0 vs 11.2 months; P = .0022). Experts have said that radium 223 will "change the standard of care" in this patient population.

MDV3100 is also for CRPC metastatic disease and, like abiraterone, targets the androgen receptor, Dr. Srinivas explained.

As previously reported by Medscape Medical News, a large phase 3 trial of MDV3100 was also stopped early when an interim analysis found a significant improvement in survival. Patients treated with the drug had a longer median survival than patients on placebo (18.4 vs 13.6 months; P < .0001).

Dr. Srinivas discussed the likelihood that abiraterone would be approved for use before treatment with docetaxel.

Currently, the drug is approved in combination with prednisone for the treatment of metastatic CRPC in men who have received previous docetaxel. Because "most patients want to delay chemotherapy," she observed, there have been "a lot of questions" and interest about giving abiraterone before chemotherapy.

A clinical trial addressing that question was just unblinded on March 8, said Dr. Srinivas. Overall and progression-free survival benefits are substantial enough to have caused the Independent Data Monitoring Committee to recommend that patients on placebo be offered the drug. FDA approval for this use is only a matter of time, she noted.

The other prostate cancer expert at NCCN said that he is impressed with the pace of change in the treatment of advanced disease. "Tremendous progress has been made in the past 2 years with new drugs," said James Mohler, MD, from the Roswell Park Cancer Institute in Buffalo, New York, who presented along with Dr. Srinivas.

However, Dr. Mohler, who is chair of the NCCN prostate cancer panel, reminded the audience that among the agents approved in the last 2 years, none has improved overall survival by more than 4.8 months. The "challenge" for clinicians is how to use the new drugs at earlier stages of prostate cancer, he said.

Sipuleucel-T for Symptomatic Men Too

The prostate cancer guidelines have some new recommendations regarding sipuleucel-T (Provenge, Dendreon) — the immunotherapy indicated for advanced disease.

Last year, the NCCN said that sipuleucel-T should be considered as a treatment option for asymptomatic men metastatic CRPC. Now, the panel says that sipuleucel-T can be used in these men who are symptomatic (a category 2A recommendation).

Whether they are symptomatic or asymptomatic, all these men with metastatic CRPC should have a good performance status (ECOG, 0 to 1) before receiving sipuleucel-T. New to the guideline is a footnote saying that this immunotherapy is not indicated in patients with an estimated life expectancy of less than 6 months and hepatic metastases.

Whether or not the change in guidance will increase the use of the immunotherapy, which has been underused relative to the grand expectations generated in the run-up to its FDA approval in 2010, is of course not known. A clinician at one NCCN center said the treatment is "fraught with logistical issues," including reimbursement matters. A sponsored lunchtime presentation at the meeting addressed the issue of reimbursement and was attended by about 50 people.

Dr. Mohler is the chief medical officer of Androbiosys.

National Comprehensive Cancer Network (NCCN) 17th Annual Conference. Presented March 15, 2011.

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