Updates in prostate cancer: ASCO GU 2014

This year marks the 10th anniversary of the oncology meeting devoted to genitourinary cancers, which includes prostate, kidney and bladder. The American Society of Clinical Oncology's Genitourinary Cancers Symposium (gucasym.org), held Jan. 30 to Feb. 1 in San Francisco, presented several studies that may impact clinical practice and future research in prostate cancer. Here are a few notable findings:Xtandi, Given Before Chemo, Extends Survival in Patients with Advanced Prostate CancerMen with advanced prostate cancer are typically given hormone therapy (androgen deprivation) until the disease progresses, whereas the next option is usually chemotherapy. Because prostate cancer is generally a slow-growing disease, delaying time to chemotherapy has been one goal in treatment. Xtandi (enzalutamide), an oral drug that blocks the androgen receptor, was approved in 2012 after it was shown to extend survival for men whose metastatic, castration-resistant prostate cancer had progressed on docetaxel. The results of the phase 3 PREVAIL study showed that when men were given Xtandi before chemotherapy, the drug delayed disease progression, improved survival, delayed time to chemotherapy and improved quality of life. The trial randomized more than 1,700 men who had few or no symptoms of their advanced prostate cancer to receive Xtandi or a placebo. Overall, Xtandi delayed the time to chemotherapy by about 17 months. Side effects were minimal and similar in both groups of patients and included fatigue, back pain, constipation and hypertension. The interim results of the study clearly showed the benefit of Xtandi, which led an independent data monitoring committee to recommend that the trial be stopped early and patients receiving placebo be offered the investigational drug. "I think it's safe to say that enzalutimde provided a significant clinical benefit to patients with metastatic castration-resistant prostate cancer," said Tomasz Beer, lead author of the study, as he concluded the presentation. After disease progression, participants in the trial went on to other therapies, including docetaxel, Zytiga (abiraterone), Jevtana (cabazitaxel), Xtandi, and Provenge (sipuleucel-T), many of which were approved in the past few years--a testament to the advances occurring in prostate cancer treatment. Yervoy in Prostate CancerResearchers presented findings from a study of Yervoy (ipilimumab), an immunotherapy that helps the body's own immune system attack the cancer. Approved for melanoma, Yervoy is being tested in several different cancer types, including prostate cancer. In this latest study, approximately 800 men with metastatic hormone-refractory prostate cancer who had already received chemotherapy were randomized to receive a placebo or immunotherapy. The study did not show an overall survival benefit, which was its primary objective. However, progression-free survival, a secondary endpoint, did show improvement with the drug. The presenting investigator noted that patients who had metastases in lung, liver or other organs did not fare well on the drug. Those who had metastasis limited to the bone fared much better, including an improvement in survival. This echoes other studies that show that immunotherapy may best be used in patients who do not have a heavy disease burden. One expert who commented on the study did suggest that may not be the whole story – it might be the different cellular environments (bone versus soft tissue metastases) that may be the deciding factor and not specifically the level of cancer metastases. Because the study did not specifically start out by stratifying patients based on the extent of their disease, it will take another study to confirm this effect. An ongoing trial is testing the drug in patients who have not yet received chemotherapy and who do not have metastases in soft organs, such as the liver or the lungs. We'll see results of that study in 2015.