Benjamin Chevalier

The PRINCE trial of Lu-177 PSMA-617 in combination with pembrolizumab has just been published @TheLancetOncol - see first comment for the link. >50% decline in PSA was observed in 76%, with >90% decline in 46%. There was more toxicity with the addition of immunotherapy including cases of colitis, pancreatitis , pneumonitis, type 1 diabetes, nephritis, myasthenia gravis, optic neuritis and mucosal pemphigus. I think Lutetium-177 PSMA "combinations" is the future of radioligand therapy, but this combination has significant toxicity. Is there a subset of biologically susceptible cancer where this combination makes sense? Thanks to @SandhuShahneen @PeterMacCC for leading this trial, and all the other investigators across multiple sites including @drlouiseemmett.

🧬 RECALIB RET 💊 Selpercatinib vs SoC (RWE EC, LIBRETTO-001) in RETmt MTC 📊 1L PFS: NR vs 26.1 mo 🔥 (p<0.001) 📊 ≥2L: signal lost post-PSM 📉 Matching attrition: −30% (1L) / −78% (≥2L) 🔎 RWE EC arms ↑ relevance 💡 Strong 1L support for selpercatinib 🔗 doi.org/10.1016/j.esmo… @OncoAlert

Co-PSMA trial #EAU26 ⁶⁴Cu-SAR-bis-PSMA PET/CT vs ⁶⁸Ga-PSMA-11 after RP (PSA 0.2–0.75 ng/mL) @urotoday @drlouiseemmett • Detection: 78% vs 36% • Mean lesions/patient: 1.26 vs 0.48 (p<0.0001) • True positive rate: 71% vs 29% Imaging changed management in 44% of pts

🚨 Gamechanger #PRIMARY2 RCT #EAU26, presented and in press @TheLancetOncol. PSMA-PET CT in men with equivocal or -ve MRI but red flags results reduces biopsy by 49% and has non-inferior csPCa detection to template biopsy in all. Proud to be part of this🚨

PCWG4 is launched: ascopubs.org/doi/10.1200/JC… Imaging response is expanded to include PSMA PET/CT. In the future, patient may have 1 scan (PSMA PET with CT) rather than two scans (CT+ bone scan). All my nuclear colleagues will be happy to retire the bone scan. @AarmstrongDuke

📢 Big win for @GrupoGetne ! AXINET: Phase III in G1–2 epNETs (n=256) 🧬 Axitinib + oct LAR vs PBO + oct LAR 📈 INV PFS 17.2 vs 13.1 mo (HR 0.86, p=NS). BICR PFS 16.6 vs 9.9 mo (HR 0.71; p=0.017) 🎯 BICR ORR 12.8% vs 3.2% ⚖️ Manageable safety (G≥3 HTN 24%) Advancing anti-angiogenic strategies in epNETs. 🔗 doi.org/10.1200/JCO-25…

Presenting data from the largest integrated thyroid cancer single-cell sequencing atlas Here, Matthew Loberg @LobergMatthew, Vivian L. Weiss @DrVivianWeiss & team @VUMChealth highlight stromal tumor-dynamics occurring across the spatial evolution of #thyroid #cancer from indolent to lethal disease, identifying a prognostic invasive cell subtype: doi.org/10.1172/jci.in… The figure shows two distinct patterns associated with anaplastic thyroid carcinoma.

🧪 Phase II: CABO + NIVO in epNETs ❌ ORR 5% (1 PR), 90% SD → did not meet Simon stage 1 threshold 📉 Median PFS 5.6 months 🛑 Manageable G3 toxicity (fatigue, transaminases, rare TLS 🔍 IO + TKI still underperforms in epNETs → need new immune strategies 🚧 🔗 doi.org/10.1158/1078-0… @OncoAlert

🔊🔊 SEQTOR trial finally published!!! Amazing international effort led by @RamonSalazarS and our great @GrupoGetne 🙌🏼🦾 @VHIO @vallhebron @ICO_oncologia Streptozotocin plus 5-fluorouracil followed by everolimus or the rever... sciencedirect.com/science/articl…

First phase 3 RLT signal in mHSPC delivered by @DrScottTagawa: 177Lu-PSMA-617 + ADT/ARPI improved rPFS vs ADT/ARPI: HR 0.72 (p=0.002). ORR 85% vs 81%; QoL similar. #ESMO25 #ProstateCancer @myESMO @Annals_Oncology @OncoAlert @OncLive

REASSURE: Combining Ra-223 + Enza in RW mCRPC pts @urotoday #ESMO25 🌀n=1,472; n=45 Ra-223 + Enza (within 30d) All pts vs Ra-223 + Enza: 🌀Any Gr AE: 37% vs 36% 🌀TE sAEs: 22% vs 20% 🌀Drug-related sAEs: 6% vs 11% 🌀mOS: 15.6 vs 19.3 mos

BULLSEYE 🎯 Ph 2 Trial (n=58): LuPSMA vs deferred ADT in omPCa @urotoday #ESMO25 @NivenMehra 🌀med F/U 27 mos, 1 SoC arm pt (3%) w/o PD vs 14 (48%) pts LuPSMA arm 🌀mPFS: 5 vs 18 mos (HR 0.07, 95% CI 0.03-0.17) 🌀TRAEs: Gr 1 xerostomia (59%), fatigue (46%), nausea (41%), bone marrow tox (25%)

TheraPb: Ph 1b Dose Esc of 212Pb-ADVC001 in PSMA+ mCRPC (n=22) @urotoday #ESMO25 🌀No DLTs, sAEs, Gr 4 TEAEs; 9% Gr 3 TRAEs 🌀@ >160 MBq: PSA50 of 80%, PSA80 of 60% 🌀6/6 ORR, 2 CRs 🌀Low normal organ rad exp, fast clearance, no relevant metabolic breakdown

177Lutetium-PSMA therapy neoadjuvant to stereotactic ablative radiotherapy for recurrent oligo-metastatic hormone-sensitive #ProstateCancer: a randomized phase 2 trial #LUNAR. Presentation by @CalaisJeremie @UCLA. #ESMO25 written coverage by @chavarriagaj @UofT > bit.ly/4orrRI2 @myESMO

First phase 3 trial exploring BRAF V600E inhibitors in DTC. #ESMO25 ➡️Dabrafenib-Trametinib vs Pbo ➡️1-2 prior MKI ⚠️PFS 12m ⚠️ORR 57% ⚠️OS NR A truly positive trial and a new option for patients with thyroid cancer 🤩🥳

The AlphaBet trial @PeterMacCC @TheLancetOncol release today @myESMO #ESMO25: combining Lu-177 PSMA-I&T + Ra-223 in men with metastatic castration-resistant #ProstateCancer is safe, feasible, and active. ✅ No dose-limiting toxicities 💪 PSA-50% decline in 55% 🧬 Supports future α+β theranostic combos. 🔗 authors.elsevier.com/a/1lyc65EIIgTS… Congrats @LouiseKostos: what an amazing PhD! Thank-you to @PCF_Science @pros_tic @Bayer for funding & support, co-senior author @AzadOncology, all the co-authors, wider village of contributors and most importantly our patients and their families for participating.

The results of the COMPETE trial (LU-177 DOTATOC vs. everolimus is mostly second line therapy (small subset 1st line). Radioligand therapy superior to everolimus. #ESMO25 @Ja_Capdevila

To operate or not on panc NETs <2 cm…? The answer is NOT. Excellent presentation by @spartelli on the long term outcomes of the ASPEN trial. Almost 1000 patients observed w/o resection and progression was uncommon, mets rare and survival the same as with resection.

📢 #ESMO25 concomitant paper: results from the phase III trial of 177Lu-Dotatate vs high-dose octreotide for advanced Grade 1-2 GEP-NETs bit.ly/48osptB

Efficacy & safety of 212Pb-DOTAMTATE in unresectable or metastatic GEP-NET previously treated with PRRT #ESMO25 #ESMOAmbassadors 👉 ORR: 34% 👉18-mo PFS: 82% 👉18-mo OS: 81% 👉Dysphagia in 57% 🧐 promising efficacy for TAT after PRRT, Dysphagia needs to be managed @myesmo