Prostate Cancer Case Studies - Episode 2
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More agents have gained FDA approval in advanced prostate cancer during the past three years than were approved in the previous two decades, mentions moderator Raoul S. Concepcion, MD. Altogether, since 2010, sipuleucel-T, abiraterone acetate, enzalutamide, cabazitaxel, and radium-223 have all gained approval to treat metastatic castration-resistant prostate cancer (mCRPC).
The oral agent abiraterone acetate (Zytiga) was initially approved in combination with prednisone to treat patients with mCRPC following progression on chemotherapy. Since this initial approval, the agent gained an expanded approval to be used before chemotherapy, an approach that Mark C. Scholz, MD, adopted early in his practice. In his experience, Scholz has found that treatment with abiraterone results in durable responses with a high quality of life and few side effects. Additionally, another recently approved oral agent, enzalutamide (Xtandi), has demonstrated similar efficacy in patients with mCRPC, Scholz adds.
These agents affect androgen through unique mechanisms of action, Scholz explains. Abiraterone eliminates residual testosterone while enzalutamide blocks androgen receptors from binding to residual testosterone, which prevents cell growth. In ways, Scholz believes, enzalutamide is an easier drug to administer, since it does not require the coadministration of prednisone.
In addition to oral antiandrogen agents, new cytotoxic approaches have also gained approval. One of these agents, labeled cabazitaxel (Jevtana), operates under a similar mechanism of action as the already approved agent docetaxel (Taxotere). This treatment is generally utilized after progression on both docetaxel and antiandrogen agents.
Leonard G. Gomella, MD, describes the immunotherapy sipuleucel-T (Provenge), which was the first autologous immunotherapy to be approved in 2010 to treat patients with minimally symptomatic or asymptomatic mCRPC. The approval was based on a 4.1-month extension in overall survival, as observed in the IMPACT trial. Additionally, Gomella states, other immunotherapeutic approaches are currently being explored in prostate cancer, including the novel fowlpox and vaccinia-based treatment PROSTVAC-VF.
In addition to the antitumor agents, a first-in-class monoclonal antibody against RANK ligand, denosmuab (Xgeva), was approved for skeletal-related events, explains Lawrence I. Karsh, MD. This agent is administered subcutaneously, does not require renal monitoring, and was shown to be more effective than zoledronic acid in clinical trials. Since its approval, denosumab has been incorporated into many treatment paradigms and bone health clinics, notes Karsh. This agent plays an important role in the treatment of bone and metabolic issues associated with LHRH agonists, adds Concepcion.