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One year following treatment with sipuleucel-T, a patient with metastatic castration-resistant prostate cancer (mCRPC) begins to shows signs of progressive disease, explains moderator, Raoul S. Concepcion, MD. His PSA has risen to 10 ng/ml, warranting repeat staging, which shows two new rib lesions by a technetium-based bone scan. The patient is taking nonsteroidal painkillers and is minimally symptomatic, Concepcion notes.
At this point, several options are available, including enzalutamide (Xtandi), docetaxel (Taxotere), and abiraterone acetate (Zytiga), explains Mark C. Scholz, MD. Traditionally, patients in this setting have been treated with docetaxel; however, the approval for abiraterone plus prednisone was recently expanded specifically to treat patients in this setting. As a result of this approval and current reimbursement models, the standard treatment in this setting is currently abiraterone, states Scholz.
Abiraterone plus prednisone was approved to treat chemotherapy-naive men with mCRPC based on results from the COU-AA-302 trial, explains Evan Y. Yu, MD. The study found a prolongation in radiographic progression-free survival (rPFS) and overall survival (OS); however, only rPFS was deemed statistically significant. The lack of significance for OS was due to several confounding factors, including an early unblinding and crossover, Yu notes.
In addition to these factors, the predefined level for significant was very low, explains Leonard G. Gomella, MD. However, an examination of the survival curves from the trial shows a clear advantage that is clinically significant, even if it is not statistically significant, Gomella believes. Additionally, Yu notes, patients lived an average of 18 months after progression on the COU-AA-302 trial. In later lines, patients received subsequent therapies that may have altered survival.
In addition to abiraterone, the pure androgen receptor blocker enzalutamide is currently under investigation as a treatment for chemotherapy-naive patients with mCRPC, explains Lawrence I. Karsh, MD. This treatment was initially approved following chemotherapy based on promising results from the AFFIRM trial and the phase III PREVAIL trial is currently exploring its earlier administration. This treatment does not require the coadministration of prednisone, which is preferential for urologists, remarks Conception.