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Enzalutamide Improved Survival in Metastatic Prostate Cancer

Goodwin, Peter M.

doi: 10.1097/01.COT.0000577060.03214.a6
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prostate cancer

prostate cancer

CHICAGO—Life was prolonged in patients with metastatic hormone-sensitive prostate cancer (mHSPC) treated with the second-generation nonsteroidal antiandrogen (NSAA) enzalutamide in addition to first-line standard-of-care therapy in the ENZAMET randomized phase III study led by the Australian and New Zealand Urogenital and Prostate (ANZUP) Cancer Trials Group and reported at the 2019 ASCO Annual Meeting (Abstract LBA2).

“Men who got the enzalutamide were 33 percent more likely to be alive [for] the duration of the study. And that translated into overall survival [increasing] from 72 percent at 3 years to 80 percent,” said study co-chair Christopher Sweeney, MBBS, Professor of Medicine at Harvard Medical School's Lark Center for Genitourinary Oncology, Dana-Farber Cancer Institute in Boston.

Christopher Sweeney, MBBS

Christopher Sweeney, MBBS

But Sweeney drew attention to the fine detail of the study results. “We saw that survival benefit was very clear in patients who did not get the concurrent docetaxel.” About 45 percent of patients on the study had chosen to receive concurrent docetaxel because it was recognized as a standard (combined with testosterone suppression)—especially for high burden disease. “So we have a split. We don't see a survival benefit in that subgroup. But we do see the survival benefit in patients with hormone-sensitive prostate cancer who don't get docetaxel,” Sweeney noted.

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Study Details

Although it had already been known that enzalutamide prolonged overall survival when used for castration-resistant prostate cancer in men who had cancer progressing with low testosterone, the researchers needed to investigate whether there would be a survival benefit when adding it to men just starting testosterone suppression for hormone-sensitive disease. “And by doing a study of men randomized to standard therapy [or] to enzalutamide, we see a significant improvement in overall survival,” he said.

In the study, 1,125 men with mHSPC were randomly assigned to receive testosterone suppression plus either enzalutamide or a standard NSAA. (Bicalutamide, nilutamide, or flutamide were the comparison standard NSAAs used in the trial.) The primary endpoint was overall survival. Subgroup analyses looked at the use (or not) of docetaxel and at high-volume compared with low-volume disease to assess any possible modulation of the treatment effect.

Overall survival was prolonged by enzalutamide. At 3 years, 36 percent of patients receiving a standard NSAA were still on their assigned study treatment as compared with 64 percent treated with enzalutamide.

Despite the lack of improvement in survival from adding enzalutamide to treatment for patients who also had docetaxel, Sweeney said there was still a role for this chemotherapy. “We know that androgen-deprivation therapy (ADT)/docetaxel/enzalutamide delays progression, but it doesn't lead to an overall survival benefit yet. So maybe the new therapies will add to the control that we see for castration-resistant prostate cancer. Or maybe they're not effective enough,” he said.

But patients treated with both ADT and docetaxel achieved “good deep remissions” and when their PSAs went up they could be salvaged by enzalutamide, Sweeney noted. “They don't have that option if the got the upfront enzalutamide.”

He said there were side effects both from the use of long-term hormones and docetaxel. “So here's what I tell people: You [come to] see me with metastatic hormone-sensitive prostate cancer. You have a high burden of disease. [If] you are fit for chemotherapy, your options are docetaxel, enzalutamide, abiraterone, or apalutamide with testosterone suppression. [There] are side effects and benefits of each approach. [But with] docetaxel, you're done in 18 weeks and you could be off the new therapies for a long time,” he said.

“But if you're not fit for chemotherapy or you have high-volume [disease, the choice is] testosterone suppression plus [one of] the new agents: enzalutamide, abiraterone, [or] apalutamide—depending on your comorbidities.”

Enzalutamide therapy increased side effects, noted Sweeney, and had to be excluded in some subgroups. He acknowledged that longer analysis was needed to assess whether there was an overall benefit from adding enzalutamide in patients receiving docetaxel. He mentioned that, as well as having its own side effects, the drug could increase docetaxel-related toxicity.

The overall conclusion was that early enzalutamide substantially improved the time to progression and overall survival when added to standard therapy in mHSPC therapy.

“Enzalutamide added to testosterone suppression represents an appropriate option for men with metastatic prostate cancer commencing testosterone suppression,” said Sweeney. “The benefit is clear in both low- and high-volume patients,” he said.

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Opinion

ASCO Expert Neeraj Agarwal, MD, Associate Professor at the Huntsman Cancer Institute's Department of Internal Medicine (Medical Oncology) in the University of Utah, Salt Lake City, commented on the findings: “We see here that giving enzalutamide early can offer worthwhile benefits—especially for certain groups of men. In addition to helping men live longer overall, this approach means they can also likely go longer without having to take steroids or receive chemotherapy.”

“Physicians and patients with prostate cancer now have a new treatment option with enzalutamide, and this is especially relevant for men who cannot tolerate chemotherapy and have a lower burden of disease seen on scans,” Sweeney also noted.

“In men with metastatic prostate cancer starting testosterone suppression, enzalutamide and docetaxel are both active and are reasonable alternatives but have different side effects, costs, risks, and benefits,” said study co-chair Ian D. Davis, PhD, from Monash University Eastern Health Clinical School in Melbourne, Australia.

Peter M. Goodwin is a contributing writer.

Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
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