onc brain

About · curated by Nick Boehling, MD · @nb2276

    2026-06-25

    digest generated 2026-06-26

    ENZARAD: 8yr MFS 74% vs 72%, HR 0.88 (p=0.34), enza added to RT+ADT misses overall; benefit isolated to cN1 / pelvic-RT pts.
    TL;DR
    Prostate carries the day's only signal. ENZARAD: enzalutamide layered on definitive RT + 2yr ADT does nothing for unselected high-risk localized disease (MFS HR 0.88, NS). Benefit confined to cN1 / pelvic-RT pts (MFS HR 0.43-0.47), but on prespecified, multiplicity-unadjusted subgroups, so hypothesis-generating.

    Prostate

    ENZARAD (ANZUP 1303)

    ForHigh-risk localized prostate, 90% Gleason 8-10, EBRT + 2yr ADT candidates

    TL;DR8yr MFS 74% vs 72%, HR 0.88 (0.67-1.15) p=0.34: adding enza to RT+2yr ADT helps nobody overall; benefit isolated to cN1/pelvic-RT pts.

    Reported via UroToday →

    vs leading data
    • vs STAMPEDE abiraterone: weaker all-comer effect, more favorable ENZARAD risk profile

    Systemic Curative Phase 3 RCT Confirmatory

    9 details
    Methods
    • 🔍 Phase III, N=802 high-risk localized, 8 countries, median f/u 8yr
    • 🔍 Arms: enza 160mg ×24mo vs active NSAA ×6mo, both on LHRH ×24mo + EBRT (active comparator, not placebo)
    • 🔍 RT: prostate 78Gy or 46Gy + brachy boost; pelvic nodes 46Gy elective + gross-node boost (40% planned, required cN1)
    Results
    • 📊 1° EP MFS negative: 8yr 74% vs 72%, HR 0.88 (0.67-1.15), p=0.34
    • 📊 Enza benefit concentrated in cN1 / pelvic-RT subgroups (prespecified, interaction-tested)
      SubgroupMFS HR (95% CI)OS HR (95% CI)
      cN10.43 (0.20-0.92)0.46 (0.17-1.26)
      Pelvic RT planned0.47 (0.29-0.76)0.53 (0.30-0.95)
      Very-high-risk0.85 (0.64-1.13)0.81 (0.57-1.13)
    • 📐 Clinical PFS favored enza: 8yr 67% vs 62%, HR 0.78 (0.61-0.99), p=0.044 (nominal)
    • 📐 OS no difference: 8yr 83% vs 80%, HR 0.87 (0.63-1.20), p=0.40 (OS was the original 1° EP)
    Critique
    • ⚠️ PFS + all subgroup HRs are nominal, unadjusted for multiplicity; prespecified but hypothesis-generating
    • ⚠️ Pelvic-RT benefit may be risk-confounded: that subgroup was 28% N1 / 62% Gleason 9/10 vs 0% N1 / 49% in no-pelvic-RT
    Open questions
    • Which pelvic-RT/cN1 subgroups truly drive enzalutamide's benefit
    • Biomarkers to select pts for ARPI intensification with RT
    • Whether nodal RT sterilization is needed to unmask the distant-met benefit
    📚 Sources · 📄 1 paper
    📄 PAPER · UroToday
    ESMO 2025: Randomized Phase III Trial of Androgen Deprivation Therapy (ADT) with Radiation Therapy with or without Enzalutamide for High Risk, Clinically Localized Prostate Cancer: ENZARAD (ANZUP 1303)
    article →
    Abstract
    ESMO 2025 ENZARAD (ANZUP 1303), randomized phase II trial of ADT + radiation therapy +/- enzalutamide, localized prostate cancer.
    📝 https://www.urotoday.com/conference-highlights/esmo-2025/esmo-2025-prostate-cancer/164090-esmo-2025-randomized-phase-iii-trial-of-androgen-deprivation-therapy-adt-with-radiation-therapy-with-or-without-enzalutamide-for-high-risk-clinically-localized-prostate-cancer-enzarad-anzup-1303.html