Anti-androgen’s benefit in chemo-naïve men tops prostate cancer news

The androgen-receptor blocker enzalutamide (XTANDI) increases survival by 29% in men with metastatic castration-resistant prostate cancer (mCRPC) and delays progression of the disease by 81%, according to new phase III study results in men who had not previously received chemotherapy.

The impressive enzalutamide findings arguably made the biggest news at the recently concluded Genitourinary Cancers Symposium in San Francisco. But there were other advances reported in advanced prostate cancer treatment, including positive findings on combination radiotherapy/anti-androgen therapy in men with locally advanced disease and evidence that prostate cancer immunotherapy results in humoral antigen spread.

Preliminary results from the phase III PREVAIL study of enzalutamide were released in October 2013 after the Independent Data Monitoring Committee recommended that the study be stopped early. The data were presented in full for the first time at the Genitourinary Cancers Symposium.

“Enzalutamide is likely to become an important new treatment option that has a significant impact on the progression of prostate cancer,” said lead author Tomasz Beer, MD, of Oregon Health and Science University, Portland. “If approved for this indication, it will become an important standard option for use before chemotherapy in patients with asymptomatic or minimally symptomatic advanced prostate cancer.”

In the double-blind, placebo-controlled study, 1,717 chemotherapy-naïve men with mCRPC were randomized to receive enzalutamide or placebo plus standard hormone therapy. Participants had previously received treatment for the primary tumor, such as surgery or radiation therapy, as well as hormone therapy with an LHRH agonist or a first-generation anti-androgen.

Results showed that enzalutamide treatment significantly reduced the risk of death by 29% (HR: 0.71, p<.0001), compared with placebo and significantly reduced the risk of radiographic progression or death by 81% versus placebo (HR: 0.19, p<.0001). In addition, on average, patients receiving enzalutamide needed chemotherapy 17 months later than those in the placebo arm.

Common side effects that were more common in the enzalutamide-treated men included fatigue, back pain, constipation, and arthralgia. Hypertension was observed in 13.4% of enzalutamide versus 4.1% of placebo-treated patients. Dr. Beer and colleagues reported zero seizures in the enzalutamide-treated group and one in the placebo group prior to the data cutoff date. One seizure was reported in the enzalutamide group after the data cutoff date.

Dr. Beer has received research funding from Astellas Pharma, Cougar Biotechnology, Janssen Biotech, and Medivation. Several study co-authors report relationships with Astellas and Medivation.

Continue to next page for additional coverage of advanced prostate cancer treatment.

Adding radiotherapy to oral anti-androgen therapy more than halved the 10- and 15-year prostate cancer-specific mortality rates in men with locally advanced prostate cancer, compared to anti-androgen therapy alone.

After nearly 8 years of observation, results published in 2009 showed a 12% reduction in prostate cancer-specific mortality in patients with locally advanced prostate cancer who initially received one injection of hormonal therapy that lasts for 3 months followed by 2 months of radiotherapy and continuous pill-based hormone therapy, compared with those who received hormone therapy alone.

In this updated analysis, after 11 years of observation, researchers reviewed mortality data from Norwegian and Swedish death registries. Among the 439 men receiving hormone therapy alone, 118 died of prostate cancer, compared with 45 out of 436 men receiving the combination treatment. For the men receiving hormone therapy alone, the 10- and 15-year prostate cancer-specific mortality rates were 18.9% and 30.7%, respectively. For those receiving the combination, these rates were 8.3% and 12.4%.

“This combination more than doubles the 10-year survival rate and confirms that this approach should be a standard option for men with this type of prostate cancer who are expected to live at least another 10 years,” said lead author Sophie Dorothea Fosså, MD, of Oslo University Hospital in Norway.

Continue to next page for coverage of sipuleucel-T.

Sipuleucel-T (Provenge) treatment may result in humoral antigen spread, a process by which the immune response broadens over time to target multiple cancer-related antigens, post-hoc subset data from the pivotal phase III IMPACT study showed.

In addition, this effect was found to be associated with improved overall survival.

"Data from the Phase III IMPACT study demonstrate that treatment with sipuleucel-T may result in humoral antigen spread, which was found to be associated with improved overall survival," said Daniel Petrylak, MD, of Yale Cancer Center, New Haven, CT. "These results are particularly exciting because they further our understanding of the sipuleucel-T mechanism of action and may enable identification of post-treatment biomarkers of clinical outcome."

Dr. Petrylak has received honoraria and research funding from Johnson & Johnson.

Look for additional coverage of these and other findings from the Genitourinary Cancers Symposium at UrologyTimes.com and in the March issue of Urology Times.

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