Kenneth J. Pienta, MD: Sequencing Therapies in mCRPC

Kenneth J. Pienta, MD, Director of Urologic Research, The Donald S. Coffey Professor of Urology, Professor of Oncology, Professor of Pharmacology and Molecular Sciences, The Johns Hopkins Hospital, explains that the first 2 therapies that should be considered are abiraterone and sipuleucel-T for patients with castration-resistant prostate cancer.

The question would be, which of these to use first, because both of them are approved for men with CRPC prior to chemotherapy. Because the patient is moderately symptomatic, abiraterone should be utilized first as the primary therapy, Pienta notes. In most cases, sipuleucel-T is reserved for those with mildly symptomatic bone lesions.

Abiraterone has demonstrated survival benefit in the prechemotherapy setting. It has been shown to have an overall survival benefit of 35 months compared with 30 months compared with placebo in men with chemotherapy-naïve CRPC. The data are very compelling that abiraterone should be used first, Pienta adds.

If the patient has a good response to abiraterone and is essentially asymptomatic, Pienta might consider sipuleucel- T. If the patient fails abiraterone, he would be eligible for docetaxel. If the patient failed chemotherapy, he would then be eligible for enzalutamide. If at any time the patient experienced bone pain from multiple lesions, he would be a candidate for radium-223, Pienta suggests.

CASE 1: Metastatic Castration-Resistant Prostate Cancer (mCRPC)

Robert C. is a 63-year-old physical education teacher and high school wrestling coach from Savannah, Georgia

In May 2007, patient presented to his PCP and received routine screening for prostate cancer.

Patient’s PSA level was 6.2 ng/mL

Digital rectal examination and subsequent CT scan revealed the presence of prostate adenocarcinoma T2bN0M0, Gleason 6 (2+4), classified as intermediate risk

Patient underwent radical prostatectomy and adjuvant radiotherapy in June 2007

Patient’s prior medical history is notable for abdominal aortic aneurysm surgery in 2002 and hypertension (well controlled on current therapy)

His liver function tests were unremarkable

In July 2010, after approximately 3 years, the patient returned to his PCP for a routine physical, and an increase in PSA to 9.7 ng/mL was detected; he was asymptomatic.

Bone scan in August 2010 was negative

Androgen deprivation therapy (ADT) was initiated in August 2010 with goserelin; the patient’s PSA subsequently decreased to 0.5 ng/mL

In September 2012, after approximately 2 years, the patient’s PSA began to rise to 2.0 ng/mL; testosterone level was 19 ng/dL

Oral bicalutamide was added to his ADT; he continued to be asymptomatic

In April 2013, the patient presented to his PCP complaining of lower back pain and moderate to severe fatigue; his PSA had increased to 3.7 ng/mL

Bone scan revealed the presence of diffuse bone lesions in the lumbar and sacral vertebral bodies