Adam B. Weiner, MD

🚨 VOLGA: chemo-free durvalumab + enfortumab vedotin beat surgery alone in muscle-invasive #bladdercancer 🚨 @NEJM today 🧵1/2 👥 n=695, cisplatin-ineligible or declined MIBC 📊 Phase 3 RCT, 1:1:1 💊 Perioperative durva + EV vs durva + tremelimumab + EV vs radical cystectomy alone ⏱️ Estimates at 24 mo ✅ Durva + EV EFS 63.5% vs 45.1%, HR 0.51 (0.38-0.67), p<0.001 ✅ OS 78.4% vs 69.4%, HR 0.58 (0.40-0.83), p=0.003 ✅ Durva + treme + EV EFS HR 0.61 (0.47-0.80), but grade ≥3 AEs 79.5% vs 71.1% ⚠️ The 2 durvalumab arms were not compared head-to-head, so the CTLA-4 add is not clearly worth the added toxicity 🎯 Another cisplatin-free ADC + IO backbone for cisplatin-ineligible MIBC

🌟Context: EV + pembro already moved the bar perioperatively. 🧵2/2 🔑KEYNOTE-905/EV-303 (cisplatin-ineligible, vs surgery): EFS HR 0.40, pCR 57% vs 9% 🔑KEYNOTE-B15/EV-304 (cisplatin-eligible, vs cis-gem): EFS HR 0.53, OS HR 0.65 👉VOLGA adds a chemo-free durva + EV option to that landscape. 🔗 https://t.co/TMEcrvUZOM @LauraBukavinaMD @UroOnc @urotoday @UrologyTimes @myESMO @DrJJZhang @AmandaNizamMD @jgong15 @UCLAHealthJCCC @Uro_Oncologist

🌟Context: EV + pembro already moved the bar perioperatively. 🧵2/2 🔑KEYNOTE-905/EV-303 (cisplatin-ineligible, vs surgery): EFS HR 0.40, pCR 57% vs 9% 🔑KEYNOTE-B15/EV-304 (cisplatin-eligible, vs cis-gem): EFS HR 0.53, OS HR 0.65 👉VOLGA adds a chemo-free durva + EV option to that landscape. 🔗 https://t.co/TMEcrvUZOM @LauraBukavinaMD @UroOnc @urotoday @UrologyTimes @myESMO @DrJJZhang @AmandaNizamMD @jgong15 @UCLAHealthJCCC @Uro_Oncologist

🚨Practice-changing in MIBC. 🚨 @NEJM 🔑KEYNOTE-B15 shows perioperative enfortumab vedotin + pembrolizumab outperformed neoadjuvant cisplatin/gemcitabine in cisplatin-eligible patients: ✅ 2-year EFS: 79.4% vs 66.2% (HR 0.53) ✅ OS: HR 0.65 ✅ pCR: 55.8% vs 32.5% ⚠️ More grade ≥3 AEs: 75.7% vs 67.2% 🏋️‍♀️After >20 years, a non-platinum perioperative regimen beats cisplatin-based chemotherapy in resectable MIBC. 🌊Alongside NIAGARA, perioperative therapy is redefining the standard of care. @SUO_YUO @UroOnc 🔗https://t.co/Zp83IldfCP

🌟Context: EV + pembro already moved the bar perioperatively. 🧵2/2 🔑KEYNOTE-905/EV-303 (cisplatin-ineligible, vs surgery): EFS HR 0.40, pCR 57% vs 9% 🔑KEYNOTE-B15/EV-304 (cisplatin-eligible, vs cis-gem): EFS HR 0.53, OS HR 0.65 👉VOLGA adds a chemo-free durva + EV option to that landscape. 🔗 https://t.co/TMEcrvUZOM @LauraBukavinaMD @UroOnc @urotoday @UrologyTimes @myESMO @DrJJZhang @AmandaNizamMD @jgong15 @UCLAHealthJCCC @Uro_Oncologist

🚨 PROTEUS: perioperative apalutamide moves into high-risk localized #prostatecancer Just out in @NEJM 🧬 2109 men w/ high-risk localized or locally advanced PCa randomized to ADT + apalutamide vs ADT + placebo around radical prostatectomy. 🎯 Both stated primary endpoints met. ⚠️ But the trial deserves nuance. Thread 🧵 #ASCO26 @ASCO @PCF_Science

🚨 TALAPRO-3: PARP inhibition moves earlier in mHSPC Just out in @NEJM 🧬 599 pts w/ metastatic HRR-altered hormone-sensitive #prostatecancer randomized to talazoparib + enzalutamide vs enzalutamide alone. 📉 52% reduction in risk of radiographic progression or death (HR 0.48, P<0.001). 3-year rPFS: 77% vs 56%. 🎯 Benefit was strongest in BRCA1/2-altered disease (HR 0.37), but remained significant in non-BRCA HRR alterations (HR 0.57). ⏳ Fewer patients required subsequent therapy (HR 0.51) and PSA progression was delayed (HR 0.51). ❤️‍🩹 OS trend favored talazoparib (HR 0.77), but data remain immature. 🩸 Toxicity remains the tradeoff: Grade ≥3 anemia in 51%, transfusions in 40%, and 2 treatment-related deaths. #ASCO26 @ASCO @PCFnews @PCF_Science @neerajaiims 🔗https://t.co/kVeRwuouKz