Cath Lab Digest

Atlanta—With the introduction of several new therapies, the treatment for castration-resistant prostate cancer (CRPC) has gone through a dramatic shift in recent years. By the end of the decade, the market for prostate cancer is expected to double, with the new agents and more in the pipeline playing an expanded role in helping patients.

The agents are effective, but are also costly, which poses some challenges for managed care professionals, according to speakers who discussed the topic during a satellite symposium at the AMCP meeting titled New Therapeutic Targets in Castration-Resistant Prostate Cancer Management.

Robert Dreicer, MD, MS, FACP, chairman of the department of solid tumor oncology at the Taussig Cancer Institute in Cleveland, Ohio, said that since the prostate-specific antigen (PSA) test was clinically introduced in 1989, the management of advanced prostate cancer has changed. Patients first receive androgen deprivation therapy before having a PSA test to assess their response. They then have biochemical progression, which is followed by secondary hormonal maneuvers and chemotherapy.

Before the PSA test, patients received hormone therapy and experienced disease progression until death.

“This is a very dramatic shift on how patients present to docs,” Dr. Dreicer said.

In the past few years, the molecular understanding of prostate cancer has improved, and more targeted therapies are available, according to Dr. Dreicer. Popular second-line hormonal therapies include antiandrogens and ketoconazole, but newer options such as lyase inhibitors and second-generation antiandrogens are other options. The US Food and Drug Administration (FDA) has recently approved several new drugs, including denosumab, sipuleucel-T, cabazitaxel, and abiraterone.

“This is a major paradigm shift in treating this disease,” Dr. Dreicer said.

In April 2011, the FDA approved abiraterone (an oral medication) after a 6-month expedited review for patients with metastatic CRPC. Dr. Dreicer discussed a phase 3 trial that enrolled 1195 patients who had failed 1 or 2 chemotherapy regimens, including one that contained docetaxel. The group taking abiraterone plus prednisone had a median overall survival of 4.6 months compared with 3.9 months for those taking placebo plus prednisone (P<.0001). An updated analysis found the abiraterone group had a median overall survival of 15.8 months, while the placebo group had a median overall survival of 11.2 months (P<.0001).

“This was a no-brainer,” Dr. Dreicer said. “Clinicians looked (at the results) and said, ‘This is the real deal.’”

Of the patients who took abiraterone, 55% had adverse events associated with elevated mineralocorticoid levels, cardiac events, and liver function test abnormalities compared with 43% of patients in the placebo group (P<.0001). However, Dr. Dreicer said using low-dose prednisone helped mitigate the adverse events.

Dr. Dreicer said abiraterone may gain broader approval in the next 6 to 12 months following the release of results from a phase 3 trial that began in April 2009. The study randomized 1000 patients in a 1:1 ratio to receive abiraterone plus prednisone or placebo plus prednisone. Patients were included if they had asymptomatic or mildly symptomatic metastatic CRPC, with the disease progressing after previous antiandrogen withdrawal.

Dr. Dreicer also cited a randomized phase 3 study comparing sipuleucel-T with placebo. Although the drug may prolong survival in patients, Dr. Dreicer said it did not improve overall response or progression-free survival and it is not a therapeutic replacement for patients who need an objective antitumor response in real time.

Another trial compared cabazitaxel plus prednisone and mitoxantrone plus prednisone in patients with metastatic CRPC.