This abstract provides data on 1,125 patients who were randomly assigned to either ENZA or NSAA. The patient arms were well balanced and stratified disease volume based on CHAARTED criteria (Low volume = less than 4 bone metastases, high volume = 4 or more bone mets with one outside the spine/pelvis and or visceral metastases, age, comorbidities, planned early docetaxel, and study site. The primary end point was overall survival, and secondary endpoints included PSA progression and clinical progression-free survival, in addition to several correlative studies. Eligibility criteria are shown below.
Baseline characteristics are shown below. Patients were well balanced by age, region, and performance status.
Volume status was well matched as well. Early docetaxel occurred in 44-45% of all patients. The volume of metastases was similar in both arms and planned skeletal-related bone therapy was similar.
In terms of the primary endpoint, overall survival was significantly improved with enzalutamide over NSAA, with an HR of 0.67 (CI .52-.86, p=0.002), with 80% of patients alive at 3 years with enzalutamide and 72% with NSAA.
Secondary endpoints showed that enzalutamide was superior for time to PSA rise, clinical progression or death (HR=0.39) and time to clinical progression (HR=0.40).
In terms of concurrent docetaxel, there was no difference in overall survival between the two arms. However, there was a benefit in clinical progression-free survival (HR=0.48).
In the following discussion by Tanya Dorff, MD, she notes that there are several significant factors (cost, length of treatment, toxicity, and volume status) to consider when choosing amongst the collection of agents now approved for mHSPC.
In terms of toxicity, the serious AE rate was similar between NSAA and enzalutamide. Notable differences included greater grade 2/3 fatigue, syncope, and seizures, all known side effects of enzalutamide and consistent with prior studies.
When enzalutamide was added to docetaxel, certain adverse events (AEs) became more common than with docetaxel alone, including grade 2 sensory neuropathy, nail discoloration, grade 1/2 watery eyes, and grade 2 fatigue.
This is the first study to show a therapy with an overall survival benefit over NSAA in the mHSPC setting. This data, along with ARCHES, support the use of enzalutamide for mHSPC. Enzalutamide may not be appropriate in certain populations such as those with a seizure history, those with significant financial toxicity, and those with debilitating fatigue at baseline, but does appear to be safe and improve overall survival for the majority of patients with mHSPC. With respect to patients receiving docetaxel chemotherapy, while there is a significant improvement in progression-free survival, data at this time does not show improved overall survival with enzalutamide and there are increased toxicities – these risks and benefits should be carefully discussed with patients before embarking on a docetaxel/enzalutamide strategy in the mHSPC setting.
Following Dr. Sweeney’s presentation, ENZAMET was published in the New England Journal of Medicine
Clinical trial information: NCT02446405
Presented By: Christopher Sweeney, MBBS, Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
Written by: Jason Zhu, MD. Fellow, Division of Hematology and Oncology, Duke University, @TheRealJasonZhu at the 2019 ASCO Annual Meeting #ASCO19, May 31- June 4, 2019, Chicago, IL USA
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