Kenneth J. Pienta, MD: Efficacy Data's Role in 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, believes that abiraterone acetate appears to be the best option for patients with symptomatic castration-resistant prostate cancer (CRPC).

When compared with placebo, abiraterone improve overall survival by 4 to 5 months. Taxotere demonstrated a small survival benefit compared with mitoxantrone in the early 2000s, and it is clear that abiraterone has a much better survival profile in these men with metastatic disease in the prechemotherapy setting. Sipuleucel-T also has a survival benefit of approximately 5 months, but abiraterone appears to be much more beneficial, Pienta notes.

At this time, the best method for measuring the response rate in the short term for sipuleucel-T is unclear. For the first treatment decision, the efficacy data push Pienta toward abiraterone. After abiraterone, Taxotere approved, and after Taxotere is no longer effective, enzalutamide is beneficial, with a survival benefit of about 5 months (13 months versus 18 months).

The radium-223 data includes a mixture of patients who showed a short survival benefit. It is effective, but it is hard to interpret the survival data. Similarly, cabazitaxel is approved in the post-Taxotere setting. It has demonstrated survival benefit compared with mitoxantrone.

The real positive note here is that multiple agents have all shown a survival benefit in the castration-resistant setting, Peinta notes. It’s a matter of sequencing, he adds.

Right now, Pienta's sequence of choice for patients with mild symptoms is to use sipuleucel-T first; otherwise, it is abiraterone to Taxotere to enzalutamide to radium-223 (as necessary), and then cabazitaxel. If patients need to be palliated, mitoxantrone is an option, but there is no survival benefit to that drug as a chemotherapy agent; it is used simply to relieve symptoms.

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