Prostate Cancer Treatments Pose Challenges for Managed Care

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. The median overall survival in the cabazitaxel group was 15.1 months, while the median overall survival in the mitoxantrone group was 12.7 months (P<.0001). Although the FDA approved cabazitaxel, Dr. Dreicer said the optimal dose has yet to be determined, and upcoming studies will compare cabazitaxel with docetaxel. In addition, a study of men with metastatic CRPC randomized patients to receive denosumab or zoledronic acid. The median time to first on-study skeletal-related event was 20.7 months in the denosumab group compared with 17.1 months for the zoledronic acid group (P=.0002 for a noninferiority analysis and P=.008 for a superiority analysis). The overall survival and overall disease progression were similar between the groups. Dr. Dreicer said next-generation drugs that may be approved to treat CRPC are XL 184 (an oral potent inhibitor of metformin and vascular endothelial growth factor-2), Src inhibitors, and combination therapies. Shetal Desai, PharmD, assistant professor at the University of Southern California School of Pharmacy, Los Angeles, discussed managed care implications associated with prostate cancer. He said the prostate cancer market will grow from $4 billion to $8.9 billion by 2019, with emerging therapies accounting for 60% of the costs. The most expensive drugs will be the intravenously administered sipuleucel-T (the first therapeutic cancer vaccine covered under the hospital outpatient and billed through Medicare Part B); cabazitaxel (injection covered under the hospital outpatient and billed through Medicare Part B); and abiraterone (oral medication covered under the retail pharmacy benefit and billed through Medicare Part D). Dr. Desai said the total treatment cost of sipuleucel-T is $93,000 compared with $48,000 for cabazitaxel, $40,000 for abiraterone, $2460 for docetaxel, and $375 for mitoxantrone. “[Sipuleucel-T, cabazitaxel, and abiraterone] have shifted our focus in prostate cancer,” Dr. Desai said. “We want to make sure the patient gets the right drug at the right time. We also understand there are cost considerations.” Because of the rising costs, payers are emphasizing outcomes and survival data to ensure the drugs benefit patients. According to Dr. Desai, the overall survival data for sipuleucel-T is 4.1 months compared with 3.9 months for abiraterone, 2.4 months for cabazitaxel, and 2.4 months for docetaxel. From a hospital perspective, Dr. Desai said there has been a shift from physician office infusions to hospital infusions. They have also adopted average sales price reimbursement, which has affected the hospitals’ ability to buy and bill. At the University of Southern California’s Norris Cancer Hospital, Dr. Desai helped implement a managed care program. From 2005 to 2007, unreimbursed oncology treatment contributed to an accumulation of debt, which led the hospital to hire a managed care pharmacist to resolve the issues, Dr. Desai added. In 2008, the hospital developed a clinical authorization center, in which clinical nurse case managers initiated payer authorization requests. Thanks to patient assistance programs, the initiative recovered $1.5 million in lost revenue. The hospital was also successful in improving reimbursement turn-around time, reducing bad debt, and decreasing disputing claims.