However, as is usually the case, there has been an ongoing effort to establish the efficacy of ENZA in the same disease space. As they have both had similar outcomes when utilized in later disease states, it is not unreasonable to expect similar outcomes when utilized in this particular patient population. To that effect, Andrew Armstrong, MD, presents the results of the ARCHES trial - a multinational, double-blind, phase 3 study (NCT02677896).
Men with metastatic hormone-sensitive PCa (mHSPC) were randomized 1:1 to ENZA (160 mg/day) + ADT or placebo (PBO) + ADT. As there has been discussion regarding the volume of disease and appropriateness of therapy, patients were stratified by disease volume (based on CHAARTED3 criteria) and prior docetaxel therapy. Full protocol listed below:
The primary endpoint was radiographic progression-free survival (rPFS) assessed centrally or death within 24 weeks of treatment discontinuation. Secondary endpoints included time to prostate-specific antigen (PSA) progression, PSA and radiographic responses and overall survival (OS). At the first analysis, final rPFS data will be presented and interim OS data. At the second analysis, final OS data will be presented (expected ~342 deaths). Treatment continued until disease progression or unacceptable toxicity.
In this study, 1150 men were randomized to ENZA (n=574) or PBO (n=576) in an intention-to-treat analysis. Baseline characteristics were balanced between groups and can be found below:
Of note, as 2 patients in each arm never received the drug, they were excluded from the safety profile analysis - ENZA (n=572) or PBO (n=574).
Overall, 67% had distant metastasis at initial diagnosis, 63%(727 men)had high volume disease, and 18% had prior docetaxel. He made a point to highlight this, as unlike the other studies in this space, prior docetaxel was allowed as part of the inclusion criteria–and patients were stratified based on prior docetaxel use.
Median follow-up was 14.4 mo. When looking at the primary endpoint, ENZA + ADT significantly improved rPFS (NR vs. 19.4 mo, HR 0.39) and similar significant improvements in rPFS were reported in prespecified subgroups of disease volume, the pattern of spread, region and prior docetaxel (HRs 0.24–0.53).
Below is the KM curve for the primary endpoint for the entire cohort:
For all subgroups (except for patients with soft-tissue only metastases), the ENZA treated patients did better, as seen below:
Even in the soft-tissue the only group, the results favored enzalutamide. Of note, he specifically highlights the fact that regardless of the volume of disease OR prior docetaxel chemotherapy, ENZA was associated with a significantly improved rPFS (HR 0.24 for low-volume and HR 0.44 for high-volume; HR 0.36 for no prior docetaxel therapy and HR 0.53 for prior docetaxel therapy).
Secondary endpoints also improved with ENZA + ADT and the full results can be found in the table below.
He briefly also reviewed the immature quality of life data –this will be further presented in detail at upcoming meetings. QOL was assessed with FACT-P assessments over the course of the study –and there was no significant difference between the groups over the length of the study, as seen below:
In general, similar to studies of ENZA in other disease states, it was well tolerated. Grade 3–4 adverse events (AEs) were reported in 24.3% of ENZA pts vs 25.6% of PBO pts with no unexpected AEs. AE’s leading to withdrawal were observed in 7.2% of the ENZA treated patients and 5.2% of the placebo-treated patients.
- There were no reports of PRES in either arm
- Ischemic cardiac disease was reported in <2% in both arms
A full summary of AE is below:
Presented by: Andrew J. Armstrong, MD, Duke Cancer Institute and the Duke Prostate and Urologic Cancer Center, Durham, North Carolina
Written by: Thenappan Chandrasekar, MD (Clinical Instructor, Thomas Jefferson University) (twitter: @tchandra_uromd, @JEFFUrology) at the 2019 American Society of Clinical Oncology Genitourinary Cancers Symposium, (ASCO GU) #GU19, February 14-16, 2019 - San Francisco, CA
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