|The following article features coverage from the American Society of Clinical Oncology 2019 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.|
Results from the ENZAMET study (ClinicalTrials.gov Identifier: NCT02446405) showed a boost in overall survival (OS) with the addition of enzalutamide, an androgen receptor inhibitor, to testosterone suppression in men with newly diagnosed metastatic prostate cancer compared with a nonsteroidal antiandrogen plus testosterone suppression. The findings of this study were reported at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.
A number of therapeutic advances for men with metastatic hormone-sensitive prostate cancer (mHSPC) have emerged within the last 5 years. For example, early use of docetaxel (6 cycles) or abiraterone, in combination with testosterone suppression, has been shown to improve OS in this population. In addition, enzalutamide was previously shown to improve radiographic progression-free survival (PFS) in men with mHSPC.
In this open-label, randomized, multinational study, patients with newly diagnosed metastatic prostate cancer were randomly assigned in a 1:1 ratio to receive first-line therapy with enzalutamide plus a luteinizing hormone-releasing analog or surgical castration (ie, testosterone suppression) compared with a conventional nonsteroidal antiandrogen (ie, bicalutamide, nilutamide, or flutamide) plus testosterone suppression. Patients enrolled in the study were allowed to also receive early docetaxel and were stratified according to whether or not this treatment was planned, as well as other factors, including whether low- or high- volume disease was present.
The study presenter, Christopher Sweeney, MBBS, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, noted that this is the first study to include a standard antiandrogen as an active control arm.
The primary end point of the ENZAMET study was OS, with secondary end points including prostate-specific antigen progression-free survival (PSA PFS), clinical PFS, and safety.
Of the 1125 men enrolled in the trial, 563 and 562 received enzalutamide or a non-steroidal antiandrogen, respectively. In both study arms, the median age was approximately 69 years, approximately 45% received early docetaxel, and slightly over 50% had high-volume disease.
At a median follow-up of 34 months, rates of 3-year OS were 80% in the enzalutamide arm versus 72% in the active control arm (hazard ratio [HR], 0.67; 95% CI, 0.52-0.86; P =.002) for the overall study population. Marked differences in PSA PFS (HR, 0.39; 95% CI, 0.33-0.47; P <.001) and clinical PFS (HR, 0.40; 95% CI, 0.33-0.49; P <.001) were also observed for the 2 study arms in the overall population.
Interestingly, the 3-year OS rates in the 2 study arms for patients receiving early docetaxel use were very similar (74% vs 75%). However, a more marked 3-year OS difference was noted for those who did not receive docetaxel (83% in the enzalutamide arm; 70% for those receiving the active control). Furthermore, the respective (ie, enzalutamide vs nonsteroidal antiandrogen) 3-year OS rates for patients with low-volume disease were 90% vs 82%, and 71% vs 64% for those with high-volume disease.
More patients on the control arm received all 6 cycles of docetaxel compared with the enzalutamide arm (76% vs 65%). Although the percentage of patients discontinuing therapy was higher for those on the control compared with the enzalutatmide arm, more patients receiving enzalutamide discontinued treatment due to adverse events (16% vs 4%).
Regarding adverse event profiles, rates of grade 2/3 hypertension and fatigue were higher for patients receiving enzalutamide, and low rates (≤5%) of falls, syncope, concentration impairment, as well as seizures (1%) were also observed for patients in this arm. In the subgroup of patients who received docetaxel, the rate of grade 2 sensory neuropathy was 3% for patients in the control arm and 9% for patients receiving enzalutamide. Interestingly, a review of the toxicity profiles suggested that enzalutamide was enhancing the toxicity of docetaxel and vice versa.
In reviewing the data regarding treatment exposure for the 2 study arms, Dr Sweeney noted that “the observed OS difference did not appear to be due to lack of access to life-prolonging treatment in [the] standard arm.”
In his concluding comments, Dr Sweeney stated that “the clinical interpretation [of these results] is that enzalutamide added to testosterone suppression represents an appropriate option for men with metastatic prostate cancer commencing testosterone suppression.”
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Sweeney C, Martin AJ, Zielinski RR, et al. Overall survival (OS) results of a phase III randomized trial of standard-of-care therapy with or without enzalutamide for metastatic hormone-sensitive prostate cancer (mHSPC): ENZAMET (ANZUP 1304), an ANZUP-led international cooperative group trial. Presented at: 2019 American Society of Clinical Oncology (ASCO) Annual Meeting; May 31-June 4, 2019; Chicago, IL. Abstract LBA2.