🚨⭐🔵 #ESMO26 | Optimising Radioligand Therapy in Advanced Prostate Cancer
🎤 Presented by @AzadOncology 🇦🇺
@OncoAlert

🔬 Beyond ¹⁷⁷Lu-PSMA: combinations, alpha emitters and the emerging promise of Auger electrons.
An excellent overview of how radioligand therapy (RLT) is evolving in #mCRPC.

📊 1️⃣ EVOLUTION: RADIOLIGANDS + DUAL IMMUNOTHERAPY

Phase II EVOLUTION (ANZUP2001):
¹⁷⁷Lu-PSMA-617 + nivolumab/ipilimumab vs ¹⁷⁷Lu-PSMA-617 alone.

✅ PSA-PFS at 12 months: 33% vs 17%
✅ rPFS at 12 months: 47% vs 23%
📈 Median rPFS: 12.0 vs 8.5 months

⚠️ However:
• Grade 3–4 AEs: 75% vs 29%
• Treatment-related myocarditis: 7% in the combination arm
• Trial recruitment stopped early.
⭐ An important reminder: biological synergy must translate into meaningful benefit without unacceptable toxicity.

💊 2️⃣ Lu-PSMA COMBINATIONS: ENCOURAGING SIGNALS
📊 PSA50 | Median rPFS | Median OS
🔹 VISION (¹⁷⁷Lu-PSMA-617 + protocol-permitted standard care): 46% | 8.7 mo | 15.3 mo

🔹 PRINCE (+ pembrolizumab, n=37): 76% | 11.2 mo | 20.8 mo
🔹 LuPARP (+ olaparib, n=29): 69% | 12.8 mo | 33.5 mo
🔹 AlphaBet (+ radium-223, n=33): 55% | 10.0 mo | 13.5 mo
🔹 LuCAB (+ cabazitaxel, n=26): 73% | 10.9 mo | 16.5 mo

⚠️ These are cross-trial descriptive comparisons, not evidence that any combination is superior to VISION. Patient selection, prior therapies and trial designs differ.

☢️ 3️⃣ ALPHA EMITTERS: A NEW LEVEL OF PRECISION

Unlike beta particles, alpha particles have shorter tissue penetration and high linear energy transfer, potentially improving tumor-cell killing.
🔬 PAnTHa: ²²⁵Ac-PSMA-Trillium
Phase I dose escalation | N=50

✅ PSA50: 58% overall
✅ PSA50: 83% at 125 kBq/kg
✅ PSA90: 58% at the expansion dose
✅ ORR: 46%
✅ Disease control: 83%
⚠️ Xerostomia: 76%
⚠️ Grade ≥3 treatment-emergent AEs: 38%
✅ No dose-limiting toxicities observed.
These preliminary results support further investigation, not routine clinical adoption.

⚛️ 4️⃣ AUGER ELECTRONS: TARGETING MICROSCOPIC DISEASE
An exciting emerging concept.
Auger electrons deposit energy over extremely short distances, potentially targeting microscopic tumor deposits and individual cells.

🔬 Terbium-161 (¹⁶¹Tb) emits beta particles and Auger/conversion electrons.
Could this improve radioligand effectiveness against micrometastatic disease?
The biological rationale is compelling, but clinical benefit remains to be demonstrated.

⭐ MY POINT OF VIEW | CLINICAL PEARL
The future of radioligand therapy will not be defined by the strongest radiation emitter, but by the right radiation strategy for the right patient.
Three essential questions remain:

🔹 Which combinations truly improve survival?
🔹 Can we intensify antitumor activity without unacceptable toxicity?
🔹 How should PSMA expression, tumor heterogeneity and disease burden guide isotope selection?
💡 Precision radioligand therapy means more than targeting PSMA: it means optimizing the payload, the partner, the timing and the patient.
From beta to alpha and Auger emitters, we are entering an exciting new era in #ProstateCancer.

@urologysummit @gbanna74 @ravikanesvaran @Uromigos @LosUromigos

@neerajaiims @Silke_Gillessen @EfstathiouEleni @AOmlin @declangmurphy @montypal @DrScottTagawa @ChrisSweens1 @brian_rini

@ecancer @UrologyTimes @urotoday @wearemedsir @OpenMedicineHQ

#GUOncology #mCRPC #PSMA #RadioligandTherapy #NuclearMedicine #PrecisionOncology