The addition of two years of Xtandi (enzalutamide) to plain androgen deprivation remedy (ADT) and high-dose radiation remedy didn’t considerably enhance metastasis-free survival (MFS) for sufferers with high-risk clinically localized or domestically superior prostate most cancers, based on information from the section 3 ENZARAD (ANZUP 1303) trial which have been shared in a presentation from the
After a median follow-up of eight years, within the general unselected inhabitants, MFS was 74% for sufferers receiving Xtandi versus 72% for these receiving a traditional non-steroidal anti-androgen (NSAA), investigators shared.
“The trial didn’t present a significant MFS profit for Xtandi in unselected high-risk localized prostate most cancers, however for sufferers with optimistic lymph nodes on computed tomography or magnetic resonance imaging or different indications for pelvic radiation, the info assist contemplating the addition of Xtandi,” Dr. Paul L. Nguyen stated within the presentation
Nguyen is at present a senior doctor and director of Genitourinary Radiation Oncology at Dana-Farber Most cancers Institute, in Boston, Massachusetts, the place he additionally serves as a professor of radiation oncology at Harvard Medical College.
Regardless of the dearth of a broad MFS profit, analysis recognized sure sufferers that derived substantial benefit from Xtandi. Amongst sufferers with scientific N1 illness, five-year MFS reached 87% with Xtandi versus 77% for NSAA, indicating that focused intensification could also be warranted in rigorously chosen sufferers.
General survival (OS) and prostate cancer-specific survival (PCSS) remained excessive throughout each examine arms, with eight-year OS at 83% versus 80% and PCSS at 97% versus 96% for Xtandi versus NSAA. Development-free survival (PFS) was modestly improved with Xtandi, with eight-year PFS of 67% versus 62%.
ENZARAD Part 3 Trial: Design and Eligibility Standards in Excessive-Threat Prostate Most cancers
The trial was designed as a global, investigator-initiated section 3 examine to find out whether or not including Xtandi to high-dose radiation and two years of ADT improves outcomes in high-risk prostate most cancers.
Contributors have been randomized to obtain both 160 milligrams (mg) of Xtandi every day for twenty-four months or standard NSAA for six months, with all sufferers receiving luteinizing hormone-releasing hormone agonist remedy for twenty-four months. Radiation remedy was delivered to the prostate at plus a brachytherapy enhance.
The trial enrolled 802 contributors throughout eight international locations from March 2014 to June 2018, with a median follow-up of eight years. Baseline traits mirrored a typical high-risk inhabitants, although solely 11% have been N1 by standard imaging. The first finish level, MFS, was assessed by standard imaging (CT, MRI, or bone scan), with prostate-specific membrane antigen–positron emission tomography-only lesions inadequate to outline occasions.
The first finish level was modified from general survival to MFS in June 2020 attributable to lower-than-expected loss of life charges in up to date trials, with occasions confirmed by a blinded central evaluate committee.
Security Outcomes from the Part 3 ENZARAD Trial
Unwanted side effects mirrored the recognized security profile of Xtandi. Grade 1/2 occasions occurred in 210 sufferers on Xtandi versus 206 NSAA sufferers, grade 3/4 in 182 versus 181, and grade 5 in 3 versus 4, respectively.
Fatigue was extra widespread within the Xtandi arm (337 sufferers grade 1/2, 16 sufferers grade 3/4) in contrast with NSAA (315 sufferers, 6 sufferers), whereas sizzling flashes have been reported in 308 versus 278 sufferers at grade 1/2. Nervous system occasions have been larger with Xtandi (177 sufferers grade 1/2, 25 sufferers grade 3/4) versus NSAA (122 sufferers, 15 sufferers), and psychiatric occasions occurred in 178 versus 169 sufferers.
Metabolic and dietary occasions, respiratory occasions, hypertension, infections, and liver enzyme elevations have been noticed in each arms, predominantly grade 1/2. Cardiac occasions, falls, fractures, thromboembolic occasions, seizures, and deaths from different causes occurred at comparable charges throughout arms.
Subgroup Analyses and Comparability to Earlier Trials
Sufferers with regional lymph node involvement skilled fewer occasions with Xtandi in contrast with NSAA, and people receiving pelvic nodal irradiation equally derived profit. Very high-risk sufferers didn’t show important interplay with therapy. Age and geographic area didn’t modify therapy impact on MFS. Exploratory analyses revealed a variety of outcomes based mostly on eligibility standards. Sufferers with scientific N1 illness and Gleason 9-10 had five-year MFS of 87% with Xtandi versus 74% with NSAA, whereas higher prognostic sufferers had five-year MFS of 86% versus 90% and OS of 90% versus 91%.
Comparisons with the STAMPEDE trial point out ENZARAD findings in N1 sufferers are according to prior outcomes utilizing Zytiga (abiraterone). Variations in baseline affected person traits clarify why the general MFS profit within the full cohort was not important.
Nguyen famous, “The profit in scientific N1 is according to STAMPEDE, however ENZARAD enrolled extra favorable sufferers, and our findings have been primarily the identical as STAMPEDE for N1 sufferers.”
Reference
- “Randomised section 3 trial of androgen deprivation remedy (ADT) with radiation remedy with or with out enzalutamide for prime threat, clinically localised prostate most cancers: ENZARAD (ANZUP 1303),” by Dr. Paul L. Nguyen. Offered at: 2025 ESMO Congress; October 17-21, 2025; Berlin, Germany. Summary LBA86.
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