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Sequencing of Novel Prostate Cancer Agents Is a Work in Progress

Jason M. Broderick
Published Online: Wednesday, December 26, 2012
William K. Oh, MD

William K. Oh, MD

Over the past decade, the availability of new agents with varying mechanisms of action has greatly enhanced the treatment landscape in castration-resistant prostate cancer (CRPC). Physicians are now tasked with determining the optimal sequencing of these diverse treatments. At the 2012 Chemotherapy Foundation Symposium, William K. Oh, MD, discussed challenges and potential strategies for treatment sequencing in patients with CRPC.

Oh, who is the chief of Hematology/Oncology at the Tisch Cancer Institute, Mount Sinai School of Medicine in New York City, identified several key questions regarding optimal sequencing:

  • Should you use immunotherapy after chemotherapy or with prednisone?
  • Can you combine androgen receptor–targeted therapies with each other or chemotherapy?
  • Is the natural progression from oral agents to IV, or is that irrelevant?
  • Are there natural synergies (or antagonisms) that should lead to rational combinations?
  • How many therapies will patients reasonably complete?
The primary challenge to answering these questions and determining a blueprint for sequencing is a paucity of data. “There is very little data to drive a rational discussion about what the answers [to these questions are],” said Oh. He added that few comparative data exist because the critical trials that examined these drugs were not head-to-head comparisons (Table). Rather, the efficacy of the drugs was established against inactive comparators—either mitoxantrone or placebo.

Table. Recent Trials in Castration-Resistant Prostate Cancer

Trial Therapy Disease State Comparator Overall Survival
Hazard Ratio P Value
IMPACT Sipuleucel-T Chemo-näive Placebo 0.775 0.032
TAX327 Docetaxel Chemo-näive Mitoxantrone 0.76 0.009
TROPIC Cabazitaxel Post-Docetaxel Mitoxantrone 0.70 <0.0001
COU-AA-301 Abiraterone acetate Post-Docetaxel Placebo 0.646 <0.0001
COU-AA-302 Abiraterone acetate Pre-Docetaxel Placebo 0.75 0.0097*
AFFIRM Enzalutamide (MDV3100) Post-Docetaxel Placebo 0.631 <0.001
ALSYMPCA Alpharadin (Radium-223) Post-Docetaxel Placebo 0.70 0.002

*Not statistically significant.

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