Treatment Strategies for Patients with Castrate-Resistant Prostate Cancer

In a session in the Oncology Track, Channing Paller, MD, presented Novel Insights on the Current and Emerging Treatment Strategies of CRPC [castration-resistant prostate cancer].

CRPC is defined as prostate-specific antigen/radiologic progression despite androgen deprivation therapy (ADT); progression despite addition of anti-androgen (AA) therapy; progression following withdrawal of AA. Patients with CRPC may have MO or M1 disease (no distant metastasis; distant metastasis, respectively).

Approved therapies for CRPC include hormonal therapies (abiraterone, enzalutamide); immunotherapy (sipuleucel-T [sip-T]); targeted radiation (radium-223); chemotherapy (docetaxel, cabazitaxel); and bone-targeted therapy (denosumab). Clinical trials are underway to test the safety and effectiveness of novel androgen receptor (AR) targeting agents (galeterone, apalutamide, TAK-700, ODM-201); poly(ADP-ribose) polymerase (PARP) inhibitors (olaparib); and immunotherapy (ipilimumab, nivolumab).

There are also clinical trials underway to test the safety and efficacy of therapies for patients with MI CRPC, including AR targeting agents (galeterone, apalutamide, ODM-201(, PARP inhibitors (olaparib), and immunotherapy (ipilimumab, nivolumab).

Treatments that are FDA-approved for patients with metastatic CRPC (mCRPC) include mitoxantrone (116, palliative benefit); docetaxel (2004, survival benefit); sip-T (April 2010, survival benefit); cabazitaxel (June 2010, survival benefit); abiraterone (April 2011, survival benefit); enzalutamide (August 2012, survival benefit); and radium-223 (May 2013, survival benefit).

There are also FDA-approved bone-targeting agents, including zoledronic acid (2002, prevention of skeletal-related events (SREs) and denosumab (November 2010, prevention of SREs). In efficacy trials, denosumab was superior (hazard ratio, 0.82 in median time to SREs). Side effects included hypocalcemia and osteonecrosis of the jaw.

Dr. Paller summarized therapies available to treat mCRPC:

• Docetaxel: treatment of symptomatic mCRPC; first-line chemotherapy agent; combined with ADT for high-volume metastatic hormone-sensitive prostate cancer (mHSPC).
• Sipuleucel-T: treatment of asymptomatic/minimally symptomatic mCRPC; first-line treatment, usually prior to docetaxel.
• Cabazitaxel: second-line therapy for mCRPC; survival benefit in patients pretreated with docetaxel.
• Abiraterone: approved for all patients with mCRPC; survival benefit in post- and pre-docetaxel patients; combined with ADT for high-volume mHSPC.
• Enzalutamide: approved for all patients with mCRPC; survival benefit in post-and pre-docetaxel patients.
• Radium-223: currently approved for mCRPC with symptomatic bone metastases (pre- or post-docetaxel); no bulky nodal or visceral metastases.

In conclusion, Dr. Paller outlined the costs of therapies for treating patients with mCRPC. Costs in US dollars were $98,860 for sip-T (4.1-month survival benefit), $61,835 for enzalutamide (3.7-month survival benefit), $43,216 for abiraterone + prednisone (3.9-month survival benefit), $16,235 for docetaxel + prednisone (2.4-month survival benefit as compared to mitoxantrone), $73.700 for radium-223 (3.6-month survival benefit), $50,038 for cabazitaxel + prednisone 2.4-month survival benefit as compared to mitoxantrone), and $71,499 for denosumab.

Channing Paller, MD. Novel Insights on the Current and Emerging Treatment Strategies of CRPC. 2017 Fall Managed Care Forum. October 27, 2017.