Major advance in combination therapy for recurrent prostate cancer

Researchers report that overall survival is significantly longer among prostate cancer patients at high-risk of biochemical recurrence who are treated with combination enzalutamide and leuprolide rather than with leuprolide alone.

The trial results were published in The New England Journal of Medicine (NEJM) with simultaneous presentation during the European Society for Medical Oncology Congress (ESMO) Oct. 19 in Berlin.

“After initial treatment, some patients see their prostate cancer come back in an aggressive way and are at risk for their disease to spread quickly,” said Stephen Freedland, MD, director of the Center for Integrated Research in Cancer and Lifestyle at Cedars-Sinai Cancer in Los Angeles and co-principal investigator of the study. “Hormone therapy, which is what we’ve been offering patients for 30 years, has not improved survival and neither has anything else. That makes these findings a real game changer.”

Over 1,000 subjects were enrolled in the study.

The investigators randomized subjects with prostate cancer and at high-risk of biochemical recurrence to receive a 1:1:1 ratio treatment with enzalutamide plus leuprolide (the combination group), leuprolide alone (the leuprolide-alone group), or enzalutamide monotherapy (the monotherapy group).

The primary end point was metastasis-free survival, assessed by a comparison of the combination group with the leuprolide-alone group.

The 8-year overall survival was 78.9% in the combination group and 69.5% in the leuprolide monotherapy group, a significant 40% difference (P<0.001).

The 8-year overall survival with enzalutamide monotherapy was 73.1% which did not differ significantly from treatment with leuprolide monotherapy (P = 0.19).

“Safety findings were consistent with those in the primary analysis of metastasis-free survival,” the authors noted.

“These important findings identify a treatment that prolongs survival in men with aggressive prostate cancer,” said Hyung Kim, MD, a urologic oncologist and chair of the Department of Urology at Cedars-Sinai.  “The latest analysis complements previous studies that found enzalutamide significantly improved survival in other prostate cancer settings, and will change how we take care of our patients.”

The authors concluded, “The final analysis of overall survival in the EMBARK trial shows that, despite prolonged treatment suspension as mandated by the protocol in the case of undetectable PSA at week 36, enzalutamide plus leuprolide resulted in longer overall survival than leuprolide alone among patients with high-risk biochemical recurrence and no evidence of metastasis on conventional imaging. These findings bolster the previously reported improvement in metastasis-free survival with enzalutamide plus leuprolide3 and further support enzalutamide plus androgen deprivation as the standard of care for patients with prostate cancer with high-risk biochemical recurrence. Finally, the results complement those of previous trials of enzalutamide in other types of prostate cancer, including castration-resistant prostate cancer and metastatic castration-sensitive prostate cancer, which showed significant improvements in survival.