Star drug enzalutamide Andrew J. Armstrong, MD, assistant professor of medicine at Duke University Cancer Institute, said that in the PREVAIL trial, enzalutamide significantly prolonged radiologic progression-free survival, significantly reduced the risk of death (by nearly 30 percent), significantly delayed cytotoxic chemotherapy, and improved FACT-P survival quality. Enzalutamide plus androgen deprivation therapy had clinically significant benefit in patients with metastatic debulking-resistant prostate cancer. The U.S. Food and Drug Administration (FDA) has approved enzalutamide for the treatment of metastatic destructive-resistant prostate cancer after treatment with docetaxel. Favorable data showing that enzalutamide is also effective in patients not treated with docetaxel will advance the use of enzalutamide for this indication. Abiraterone (Zytiga), another drug that targets the androgen receptor, is currently FDA-approved for use before and after chemotherapy for metastatic destructive-resistant prostate cancer. Dr. Armstrong updated the overall survival data, finding no median survival at 26 months of follow-up in the enzalutamide treatment arm and 31 months in the placebo arm. Enzalutamide significantly delayed the start of chemotherapy and significantly optimized the prostate-specific antigen (PSA) response rate, time to PSA progression, objective soft tissue response rate, and time to first bone-related event. For quality of life issues, Dr. Armstrong said during the meeting that the quality of life response rate in the enzalutamide treatment group was nearly 40%, compared to 22.9% in the placebo group. Enzalutamide significantly improved the quality of life of patients compared to the placebo group in all aspects of the FACT-P consideration. The enzalutamide-treated group was associated with an increased risk of fatigue, hot flashes, and falls. Grade 3 or higher hypertension was reported in 6 percent of patients in the enzalutamide group and 2.3 percent in the placebo group. The incidence of cardiovascular events was similar in both groups. orteronel improves progression-free survival The large international phase III ELM-PC 4 study showed that orteronel plus prednisone treatment significantly improved radiologic progression-free survival in patients with chemoresistant prostate cancer without chemotherapy; however, orteronel failed to improve overall survival (the primary endpoint). According to Ronald de Wit, MD, PhD, professor in the Department of Medical Oncology at Erasmus University Medical Center in Rotterdam, the Netherlands, the ELM-PC 5 trial also showed that orteronel improved radiologically progression-free survival but not overall survival; subsequent subgroup analyses of the trial showed that survival appeared to improve in the non-European/North American population from the ELM-PC 4 study, while overall survival No regional differences were observed. orteronel is an investigational reversible selective inhibitor of the non-steroidal 17, 20 cleavage enzyme whose activity is upregulated in patients with destructive-resistant prostate cancer. The ELM-PC 4 trial included 1560 chemotherapy-free, opioid-free patients with metastatic destructive-resistant prostate cancer from 43 different countries who were randomized to receive orteronel 400 mg twice daily in combination with prednisone 5 mg twice daily or placebo + prednisone in a 1:1 ratio. The primary endpoints of the trial were progression-free survival as indicated by imaging and overall survival. One-fifth of patients discontinued treatment at 12 weeks of orteronel treatment, with a higher incidence of adverse events in the orteronel group. 30% of discontinuations were due to adverse events, with fatigue being the most common cause. Other common side effects included gastrointestinal adverse events (nausea, vomiting, diarrhea), fatigue, malaise, heart disease, and increased lipase and amylase levels. Cetumumab disappoints The Southwest Oncology Group (SWOG) S0925 randomized study included 211 patients with metastatic hormone-sensitive prostate cancer and found that the addition of cetumumumab (an investigational monoclonal antibody drug that acts on the insulin-like growth factor type 1 receptor (IGF-1R)) to bicalutamide and luteinizing hormone-releasing hormone agonist androgen deprivation therapy compared to androgen deprivation monotherapy (IGF-1R)) failed to meet the primary endpoint of the trial (undetectable PSA levels, e.g., ≤0.2 ng/nL). At week 28, the proportion of patients achieving undetectable PSA levels was 40% in the sitosterol-added group and 32.4% in the androgen deprivation group. The proportion of patients with grade 1, 2 and 3 hyperglycemia was 27.7%, 14.9% and 7.9% in the cetomax-plus group and 7.7%, 0% and 0% in the androgen deprivation monotherapy group, respectively.