The Lynx Group

New Drugs for the Treatment of Prostate Cancer

October 2012, Vol 3, No 7

Vienna, Austria—Promising preliminary results for 2 novel prostate can-cer drugs—ODM-201 and OGX-427—were reported at the 2012 European Society for Medical Oncology Congress. Both drugs were studied for the treatment of castration-resistant prostate cancer (CRPC).

ODM-201

ODM-201 (Orion Pharmaceuticals, Endo Pharmaceuticals) is a novel androgen receptor antagonist. In a proof-of-concept, first-in-man study, ODM-201 reduced levels of prostate-specific antigen (PSA) in men with progressive metastatic CRPC. In this dose-escalation trial, 87% (N = 15) of patients experienced a decrease in PSA level at 12 weeks. All 6 patients who were pretreated with docetaxel achieved a decrease in PSA at 12 weeks. All evaluable patients had a partial response or stable disease at 12 weeks.

“These early results are promising. ODM-201 may prove to be a new hormonal treatment option, and its efficacy and safety profile seems to be very promising in prostate cancer patients,” said lead author Christophe Massard, MD, Department of Medical Oncology, Institut Gustave Roussy, Villejuif, Paris, France. “Of course, this will need to be confirmed in larger trials.”

Preclinical data with this novel androgen receptor antagonist showed that the drug does not penetrate the brain and does not have partial agonist activity, as is observed with another hormonal agent, bicalutamide. The tolerability of ODM-201 was good.

The formal discussant of this poster, Joan Carles, MD, PhD, of Vall d’Hebron University Hospital, Barcelona, Spain, said that, compared with enzalutamide (also known as MDV3100), ODM-201 achieved better PSA responses and was associated with less toxicity, including less diarrhea and asthenia. In addition, ODM-201 does not appear to carry any risk of seizure.

“The weakness of this study is that there are few patients, and the recommended dose for phase 2 and 3 trials is not clear,” Dr Carles noted.

OGX-427

Results from the phase 1 portion of a planned phase 1/2 trial focused on OGX-427 (OncoGenex Pharmaceuticals), a heat shock protein inhibitor, according to a poster by Kim N. Chi, MD, Senior Scientist and Clinical Associate Professor of Medicine at BC Cancer Agency, Vancouver, Canada, and colleagues. The phase 2 component of this trial is ongoing. OGX-427 is also in other ongoing phase 2 studies, one in combination with abiraterone for patients with CRPC and one in combination with gemcitabine and cisplatin for patients with bladder cancer.

Patients with metastatic CRPC were randomized to OGX-427 plus prednisone (n = 17) or to prednisone alone (n = 16). Crossover at disease progression was allowed.

Treatment with OGX-427 demonstrated antitumor activity, with a response rate of 25% versus 12% for prednisone alone. Decreases in PSA of ≥50% were observed in 47% of patients treated with OGX-427 plus prednisone versus in 21% of patients who received prednisone alone.

The drug achieved a delay in disease progression and was generally well tolerated, with adverse events predominantly seen as grades 1 and 2 infusion-related reactions. Grades 1 and 2 diarrhea, fatigue, and nausea were also observed. Most adverse events were reported during the first or second administration of the drug.

Dr Carles pointed out that ODM-201 and OGX-427 represent potential new agents for the treatment of CRPC. Going forward, the challenge will be to choose the best treatment option and to determine the optimal combinations and sequencing of several new, effective drugs that have become available in the past few years.

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