🚨⭐🟠 #ESMO26 | Abstract 4757RO | GDFATHER-NEO @OncoAlert @myESMO Final pathological and radiological outcomes and initial EFS from a blinded, exploratory phase 2 trial of nivolumab ± visugromab in MIBC (GDFATHER-NEO) 🎤 Presented by @AndreaNecchi 🇮🇹 @OncoAlert @myESMO 🔬 Can targeting GDF-15 overcome resistance to PD-1 blockade in muscle-invasive bladder cancer? Exciting updated results, simultaneously published in Nature Medicine! 📖 🧬 THE SCIENTIFIC RATIONALE GDF-15 is an immunosuppressive cytokine implicated in resistance to checkpoint inhibition. Visugromab, a GDF-15-neutralizing antibody, may help restore antitumor immune activity and enhance nivolumab efficacy. 📊 STUDY DESIGN Blinded, exploratory phase II | N=31 Patients with cisplatin-ineligible or cisplatin-refusing MIBC (cT2–T4aN0M0). 🟠 Nivolumab + visugromab 🔵 Nivolumab + placebo 28 patients evaluable for efficacy (15 vs 13). 📊 KEY RESULTS ✅ Pathological complete response (pCR) 33.3% vs 7.7% ✅ Major pathological response (MPR) 60.0% vs 23.1% ✅ Radiographic ORR 60.0% vs 15.4% 📌 Consistent improvements across pathological and radiological endpoints. 🧬 EVENT-FREE SURVIVAL & BLADDER PRESERVATION At a median follow-up of 15.7 months: ✅ No recurrences among the 6 patients achieving pCR (5 vs 1). ✅ Four of five patients with pCR in the combination arm retained their bladder following re-TURBT alone. 📈 Median EFS was not reached in either arm. ⚠️ Follow-up remains limited, and durable EFS or bladder-preservation benefit has not yet been established. 🛡️ SAFETY ✅ No new safety signals. ✅ No treatment-related discontinuations or delays to surgery in the combination arm. 🧬 BIOMARKER INSIGHTS Baseline proliferating CD8+ T-cell infiltration correlated with response to nivolumab + visugromab. A promising biological signal supporting further investigation of GDF-15-mediated immune resistance. ⭐ MY POINT OF VIEW | CLINICAL PEARL What makes GDFATHER-NEO particularly interesting is not simply the improvement in pCR, but the possibility of overcoming an immunosuppressive mechanism limiting PD-1 activity. However, recent perioperative MIBC trials remind us that higher pathological response rates do not automatically translate into better EFS or OS. 💡 Can GDF-15 blockade help identify a biologically selected population for effective, less invasive treatment? That is the question worth pursuing. 📌 For now, this is promising proof-of-concept—not a new standard of care or sufficient evidence to omit cystectomy. Larger prospective trials, validated biomarkers and longer follow-up are essential. 👏 Congratulations to @AndreaNecchi, Chiara Mercinelli, Felix S. Lichtenegger and all co-authors on the Nature Medicine publication! @urologysummit @gbanna74 @ravikanesvaran @Uromigos @LosUromigos @tompowles1 @PGrivasMDPhD @apolo_andrea @sonpavde @drenriquegrande @shilpaonc @MattGalsky @ecancer @UrologyTimes @urotoday @wearemedsir @OpenMedicineHQ #BladderCancer #MIBC #GDF15 #Immunotherapy #GUOncology #PrecisionOncology

🚨⭐🔵 #ESMO26 | Abstract 2215O | PEACE-1 Long-term overall survival with abiraterone acetate plus prednisone in the PEACE-1 phase 3 trial for de novo metastatic castration-sensitive prostate cancer (mCSPC) 🎤 Presented by Prof. Karim Fizazi 🇫🇷 @OncoAlert @myESMO 🔬 7.7 years of follow-up: Does upfront treatment intensification translate into durable survival? PEACE-1 provides a compelling answer! 📊 PHASE III | N=1,173 Randomized 2×2 factorial design evaluating abiraterone + prednisone and/or prostate radiotherapy added to standard of care (ADT ± docetaxel). Median follow-up: 7.7 years. 📈 1️⃣ OVERALL POPULATION ✅ OS HR 0.75 (95% CI 0.65–0.87) ✅ p=0.0001 Median OS: 🔹 With abiraterone: 6.1 years 🔹 Without abiraterone: 4.6 years ➡️ A sustained 25% relative reduction in the hazard of death. 💥 2️⃣ TRIPLET THERAPY | N=710 ADT + docetaxel + abiraterone vs ADT + docetaxel: ✅ Median OS: 6.2 vs 4.4 years ✅ HR 0.68 (95% CI 0.56–0.82) ⭐ 1.8 additional years in median survival! 📊 8-YEAR OVERALL SURVIVAL ✅ Triplet: 40.3% 🔹 Doublet: 27.1% ➡️ Absolute difference: +13.2 percentage points. These are clinically meaningful long-term outcomes, beyond early response rates or surrogate endpoints. 🔬 3️⃣ DOES METASTATIC VOLUME MATTER? 🔵 HIGH-VOLUME DISEASE ✅ Median OS: 4.6 vs 3.5 years ✅ HR approximately 0.68 A clear and durable survival advantage. 🔵 LOW-VOLUME DISEASE 📈 Median OS: 7.8 vs 6.2 years HR 0.74 (95% CI 0.52–1.05) Numerically favorable, although the subgroup CI crossed 1. 📌 No significant interaction by disease volume (p=0.56). ⚠️ This does not establish identical treatment benefit in both subgroups. ⭐ MY POINT OF VIEW | CLINICAL PEARL Long-term follow-up is where a treatment strategy proves its true value. Unlike early response signals, PEACE-1 provides mature evidence that upfront systemic intensification can translate into substantially longer survival. 💡 In appropriately selected patients with de novo mCSPC who are candidates for docetaxel, these findings strongly reinforce the role of upfront triplet therapy. The clinical question is increasingly not simply whether to intensify, but which patients should receive a triplet, how best to integrate local treatment, and how to preserve quality of life. 🎯 Precision matters—but so does acting early when a proven survival advantage is available. 👏 Congratulations to Prof. Karim Fizazi and the entire PEACE-1 team for this important long-term contribution to prostate cancer care! @urologysummit @gbanna74 @ravikanesvaran @Uromigos @LosUromigos @neerajaiims @Silke_Gillessen @EfstathiouEleni @AOmlin @declangmurphy @cdanicas @montypal @DrScottTagawa @ecancer @UrologyTimes @urotoday @wearemedsir @OpenMedicineHQ #ProstateCancer #mCSPC #mHSPC #GUOncology #PEACE1 #TripletTherapy

🚨⭐🟠 #ESMO26 | Day 2 | Abstract 4741RO | NIAGARA Exploratory Analysis of Molecular Subtypes and Association With Treatment Outcomes in Muscle-Invasive Bladder Cancer 🎤 Excellent presentation by @MattGalsky 🇺🇸 @OncoAlert @myESMO 🧬 Does tumor biology influence the benefit of perioperative durvalumab in MIBC? 🔬 STUDY DESIGN Phase III NIAGARA | N=1,063 Perioperative durvalumab + neoadjuvant gemcitabine/cisplatin vs chemotherapy alone, followed by radical cystectomy. Exploratory molecular analysis: ✅ Whole-exome sequencing: n=407 ✅ RNA sequencing: n=402 📊 KEY MOLECULAR FINDINGS 🔹 Broad EFS benefit: Durvalumab-containing treatment favored EFS across multiple mutation-defined subgroups. 🔹 Genomic alterations: Greater apparent benefit was observed in tumors harboring TP53 or FGFR3 mutations, cell-cycle or RTK/RAS/PI3K pathway alterations, and high tumor mutational burden. 🔹 Basal-squamous subtype: Showed one of the strongest exploratory signals of benefit, with increased immune-infiltration signatures. 🔹 Luminal-papillary subtype: The EFS benefit appeared less evident than in other transcriptomic subtypes. ⚠️ These findings are exploratory. No molecular subtype has been prospectively validated to predict differential benefit from perioperative durvalumab. ⭐ MY POINT OF VIEW | CLINICAL PEARL Molecular heterogeneity may influence the magnitude of benefit, but it should not yet determine who receives potentially curative perioperative immunotherapy. 🧬 The real opportunity is moving from molecular classification toward clinically validated predictive biomarkers. 💡 The future is not simply knowing the tumor subtype—it is knowing how to act on it without compromising cure. Congratulations to @MattGalsky and the NIAGARA investigators for this insightful translational analysis! @urologysummit @gbanna74 @ravikanesvaran @Uromigos @LosUromigos @tompowles1 @PGrivasMDPhD @apolo_andrea @AndreaNecchi @sonpavde @drenriquegrande @montypal @ecancer @UrologyTimes @urotoday @wearemedsir @OpenMedicineHQ #BladderCancer #MIBC #GUOncology #PrecisionOncology #Biomarkers

🚨⭐🟠 #ESMO26 | Day 2 | Abstract 4740RO | EV-103 / KEYNOTE-869 Long-Term Follow-up of Enfortumab Vedotin ± Pembrolizumab in Cisplatin-Ineligible Advanced or Metastatic Urothelial Cancer 🎤 Excellent presentation by @Maroto5Pablo 🇪🇸 @OncoAlert @myESMO 🔬 How durable is the benefit of first-line EV + pembrolizumab? Updated phase Ib/II EV-103 findings provide valuable long-term evidence in #UrothelialCancer. 📊 STUDY DESIGN • EV + pembrolizumab: n=121 (pooled DE/A/K cohorts) • EV monotherapy: n=73 (cohort K) • Cisplatin-ineligible, previously untreated la/mUC Median survival follow-up: 🔹 EV + pembro: 64.2 months 🔹 EV alone: 58.6 months 📈 KEY EFFICACY RESULTS | EV + PEMBROLIZUMAB ✅ Median duration of response: 29.6 months (95% CI 10.3–71.9) ✅ Median PFS: 10.4 months (95% CI 8.3–20.9) ✅ Median OS: 27.7 months (95% CI 20.9–39.6) ⭐ 5-YEAR SURVIVAL • Estimated OS: 33.0% • Estimated PFS: 24.3% At 7 years, estimated OS remained 28.2%. 📌 Sustained responses and long-term survival in a historically difficult-to-treat population. ⚠️ SAFETY & TOLERABILITY Grade ≥3 treatment-related AEs: • EV + pembro: 64.5% • EV alone: 47.9% No new safety signals were identified. However, peripheral neuropathy remains an important consideration, particularly with prolonged survivorship. ⚠️ No formal statistical comparisons between cohort K treatment arms were planned. These results should not be interpreted as a randomized demonstration of superiority. ⭐ MY POINT OF VIEW | CLINICAL PEARL Durability is what transforms an impressive initial response into meaningful long-term clinical benefit. EV-103 provides important mature follow-up supporting the sustained activity of EV + pembrolizumab, while EV-302 provides the randomized evidence underpinning its first-line standard-of-care role. 💡 As more patients achieve prolonged survival, managing cumulative toxicity becomes just as important as achieving tumor response. The next challenge is optimizing treatment duration, toxicity management and sequencing while preserving long-term benefit and quality of life. 👏 Congratulations to @Maroto5Pablo and all EV-103 investigators! @urologysummit @gbanna74 @ravikanesvaran @Uromigos @LosUromigos @tompowles1 @PGrivasMDPhD @apolo_andrea @AndreaNecchi @sonpavde @drenriquegrande @montypal @ecancer @UrologyTimes @urotoday @wearemedsir @OpenMedicineHQ #BladderCancer #GUOncology #ADC #EV103 #Immunotherapy

🚨⭐🔵 #ESMO26 | Abstract 2045O | STAMPEDE / Decipher Transcriptome Classifier Risk Stratification and Intensification With Androgen Receptor Pathway Inhibitors for Clinically Very High-Risk Prostate Cancer 🎤 Excellent presentation by Dr. Sarah Howlett 🇬🇧 @OncoAlert @myESMO 🧬 Can Decipher help identify who truly benefits from abiraterone intensification in high-risk M0 prostate cancer? An important step toward biologically guided treatment decisions! 📊 STUDY DESIGN Retrospective biomarker analysis of the randomized phase III STAMPEDE trial. 👥 N=401 patients: 🔹 ADT alone: n=208 🔹 ADT + abiraterone/prednisolone: n=193 Complemented by a large real-world genomic dataset. 🔬 KEY RESULTS 🧬 1️⃣ DECIPHER IS PROGNOSTIC Higher Decipher scores were associated with increased risk of distant metastasis and worse overall survival. In the STAMPEDE ADT-alone arm, each 0.1-point increase in Decipher score was associated with: 📈 Distant metastasis: aHR 1.44 (95% CI 1.19–1.76). 🎯 2️⃣ DECIPHER MAY PREDICT ABIRATERONE BENEFIT A significant treatment-by-biomarker interaction was observed for distant metastasis: ✅ Interaction p=0.03 📊 Absolute reduction in distant metastasis at 5 years: 🔹 Lower Decipher (<0.60): 2 percentage points ✅ High Decipher (0.60–0.85): 12 percentage points ✅ Very high Decipher (>0.85): 8 percentage points 📌 Patients with higher genomic risk appeared to derive greater absolute benefit from treatment intensification. 🔬 A particularly relevant predictive signal was observed in node-negative patients. ⚠️ No statistically significant treatment-by-Decipher interaction was established for OS. ⭐ MY POINT OF VIEW | CLINICAL PEARL Clinical high-risk disease is not necessarily biologically homogeneous. The key innovation is moving beyond Decipher as a prognostic classifier toward its potential use as a predictive biomarker for treatment intensification. 💡 The future is not simply identifying who is at greater risk, but identifying who gains the greatest absolute benefit from additional treatment. However, these retrospective findings do not yet justify withholding abiraterone solely because of a low Decipher score. 🎯 Precision intensification—and eventually evidence-based de-escalation—will require prospective validation. Congratulations to Sarah Howlett and the STAMPEDE investigators! 👏⭐ @urologysummit @gbanna74 @ravikanesvaran @Uromigos @LosUromigos @neerajaiims @Silke_Gillessen @EfstathiouEleni @AOmlin @declangmurphy @cdanicas @montypal @DrScottTagawa @ecancer @UrologyTimes @urotoday @wearemedsir @OpenMedicineHQ #ProstateCancer #STAMPEDE #Decipher #PrecisionOncology #GUOncology