VOLGA (NCT04960709, AstraZeneca) is the Phase 3 trial of perioperative durvalumab plus 3 cycles of neoadjuvant enfortumab vedotin (EV), with or without tremelimumab, versus radical cystectomy with observation or locally approved adjuvant treatment (control) in muscle-invasive bladder cancer ineligible for or refusing cisplatin (N=695). At ESMO 2026 (LBA2, Oct 24, 2026; data cut-off 2 March 2026), durvalumab + EV improved event-free survival (HR 0.51) and overall survival (HR 0.58) versus control. Investigational; FDA Priority Review for durvalumab + EV.
Discover KOL Sentiment on VOLGA →Read AstraZeneca Topline →Posts by physicians about VOLGA, newest first: ESMO 2026 week (October 17–24, 2026), then earlier posts back to the May 14, 2026 topline announcement. Each post is shown in full and verbatim and linked to the original on X.
𝕏💔 EV has a new partner! PEMBRO: “Another checkpoint inhibitor?!” 😳 EV: “We have survival data TOO!” ❤️ 🔥 VOLGA | ESMO 2026 EFS HR 0.51 | OS HR 0.58 But PEMBRO isn't out of the picture! KEYNOTE-905: EFS HR 0.40 | OS HR 0.50 Two promising perioperative partnerships in cisplatin-ineligible MIBC. ⚠️ Different trials. No head-to-head comparison. @myESMO @OncoAlert #MVOnco #ESMO2026 #BladderCancer
𝕏IO + EV upfront is now the SoC for MIBC!! But how much EV do we need in postOP settings? Eagerly looking forward to more data/discussion on Day 2 #ESMO26! VOLGA as the new SoC!!??!! #gusm @myESMO #BladderCancer https://t.co/vuu0mlgkY7 https://t.co/TQSEm2YESX
𝕏KEYNOTE-905 vs VOLGA | EV has two partners in MIBC! Both perioperative strategies improve EFS and OS in cisplatin-ineligible MIBC. 🔹 KEYNOTE-905: EV + pembrolizumab, with postoperative EV. 🔹 VOLGA: EV + durvalumab, without postoperative EV. The key difference? Postoperative EV — 6 cycles vs NONE! ⚠️ Different trials, different designs. Cross-trial comparisons cannot establish superiority. @myESMO @OncoAlert #ESMO26 #BladderCancer #MIBC #MVOnco
𝕏With VOLGA results coming at #ESMO26, a summary of contemporary phase III perioperative trials in muscle-invasive bladder cancer. ⚠️ Different populations and designs—avoid cross-trial comparisons. VOLGA and EV-303 importantly include surgery-alone control arms without neoadjuvant therapy. 🔑 The next challenge: identifying who truly needs adjuvant ADC therapy—and who can safely avoid it. #BladderCancer #GUOnc @OncoAlert @BladderCancerUS
𝕏🚨 VOLGA is positive! But how much perioperative EV do we really need in MIBC? Interesting comparison with KEYNOTE-905 at #ESMO26: 🔹 VOLGA (EV + durvalumab): 2-year EFS 64%, OS 78%, pCR 45%. EFS HR 0.51. 🔹 KEYNOTE-905 (EV + pembrolizumab): 2-year EFS 74.7%, OS 79.7%, pCR 57.1%. EFS HR 0.40. Numerically lower EFS and pCR in VOLGA. Why? Different patient populations and tumor characteristics? Different study designs? It seems premature to attribute these differences to pembrolizumab vs durvalumab. But the most intriguing question is how much benefit does adjuvant EV actually add? VOLGA achieved a significant OS benefit with just 3 neoadjuvant EV cycles and NO adjuvant EV, whereas KEYNOTE-905 planned 9 EV cycles (3 neoadjuvant + 6 adjuvant)—and fewer than half of patients reportedly completed the full planned EV course. Could pCR and ctDNA clearance help us safely omit adjuvant EV and reduce cumulative toxicity? ⚠️ Cross-trial comparisons are hypothesis-generating, not evidence of superiority or equivalence. Only prospective trials can establish the incremental benefit of adjuvant EV. More EV ≠ necessarily better outcomes. Let’s identify who really needs it! 🔬 @OncoAlert @weoncologists @tompowles1 @urotoday @Uromigos @OncoAlert Faculty @DrChoueiri , @tompowles1 , @apolo_andrea , @neerajaiims , @montypal , @Silke_Gillessen , @AOmlin , @brian_rini , @PGrivasMDPhD , @TiansterZhang , @amerseburger , @DrDanielHeng , @HHammersMD , @scocmem , @AndreaNecchi , @AmandaNizamMD , @drenriquegrande , @nataliagandur , @AlbigesL , @cdanicas , @declangmurphy , @seanmmcbride , @shilpaonc , @DrRanaMcKay , @scserendipity1 , @DrYukselUrun , @ravikanesvaran , @BraunMDPhD , @EfstathiouEleni , @mzugman , @crisbergerot @Markuseckstein3
𝕏🚨 VOLGA | ESMO 2026 | LBA2 A major advance in cisplatin-ineligible muscle-invasive bladder cancer! 💚 EV + durvalumab significantly improved survival: 📊 EFS: HR 0.51 | 24-month 64% vs 45% 📊 OS: HR 0.58 | 24-month 78% vs 69% 🔥 The key distinction: EV was given ONLY before surgery — NO postoperative EV! 🤔 Does tremelimumab add meaningful benefit? Is adjuvant durvalumab essential? Can treatment eventually be de-escalated? Impressive survival benefit. Important questions remain. @myESMO @OncoAlert @larvol #ESMO26 #VOLGA #BladderCancer #MVOnco
𝕏The #ESMO26 Presidential Symposium is about to begin! 🔥 Super excited to hear the highly anticipated results of the VOLGA trial, presented by the the only and only @tompowles1! @myESMO @apolo_andrea @Uromigos @brian_rini @OncoAlert @LosUromigos @uromigosjapan @MichvdHeijden
𝕏🆙#ESMO26 Presidential Symposium I 🔥VOLGA: Perioperative Durvalumab With or Without Tremelimumab Plus Neoadjuvant Enfortumab Vedotin in Muscle-Invasive Bladder Cancer: Results From the Phase 3 Trial 🎙️ @tompowles1 🔢LBA2 🎯Durva+EV: Significantly Improved EFS (HR 0.51, 24-Mo 64% vs 45%) and OS (HR 0.58, p=0.0027) vs Control (n=233 vs 229) 🎯pCR 45% vs 10%; Durva+Treme+EV: EFS HR 0.61, OS Not Significant ☑️NCT04960709 🔗 https://t.co/t988kyrR7h @OncoAlert @Larvol @myESMO
𝕏VOLGA explored short periods of EV (3 cycles) with duvalumab in muscle invasive bladder cancer #ESMO26 @NEJM. Results showed EVD was associated with better EFS + OS vs cystectomy alone (0.51 and 0.58 respectively). pCR 40-45% with ctDNA clearance rates of 60%. High rates of adjuvant IO therapy uptake and low rates of neuropathy suggest potential advantages of this approach which focuses the ADC in the neoadjuvant phase. It’s likely to be attractive for patients.
𝕏ctDNA analysis is an increasingly utilised prognostic tool in muscle invasive bladder cancer. In VOLGA 78% of the muscle invasive bladder cancer patients were ctDNA positive at baseline which was prognostic. Also, the combination of perioperative durvalumab and neoadjuvant EV cleared ctDNA in 60% of patients (using the Natera Genome assay which has increased sensitivity). Clearance was associated with much better outcomes. #ESMO26
𝕏Excellent presentation by @tompowles1! VOLGA: perioperative durvalumab + 3 cycles of neoadjuvant EV improved EFS (HR 0.51) and OS (HR 0.58) vs cystectomy ± adjuvant therapy in cisplatin-ineligible/declining MIBC. ADCs moving earlier! #ESMO26 @oncoalert @myESMO https://t.co/ex3NdpxzoI
𝕏VOLGA also explored short periods of EV with duvalumab and tremelimumab in muscle invasive bladder cancer #ESMO26 @NEJM. Results showed EVDT improved EFS vs cystectomy (HR 0.61). Significant OS was not reached at this interim (HR 0.77 -ongoing analysis). EVDT = 10% higher rates of G3/4 toxicity and less EV delivery than the EV durvalumab arm. More is not always better. It appears the addition of treme partly compromised delivery of EV, which likely accounts for the more modest results compared to the doublet @OncoAlert
𝕏Presidential Session ➡️ @NEJM ➡️ your screen. Our Amazing @OncoAlert faculty @tompowles1 🇬🇧breaks down VOLGA: perioperative durva + neoadjuvant EV improves EFS and OS in cisplatin-ineligible MIBC. Kudos to Dr. Powles and team on the great trial, presentation and NEJM publication A must-watch 🎥👇 #ESMO26 #Podium2Screen #BladderCancer
𝕏#ESMO26 | VOLGA Neoadjuvant EV + perioperative durvalumab demonstrated impressive results in MIBC✅ An important detail: Approximately 25% of patients were not cisplatin-ineligible but had refused cisplatin. Therefore, the potential role of this regimen may extend beyond cisplatin-ineligible patients
𝕏Fantastic presentation by @tompowles1 @Uromigos on VOLGA trial showing practice changing EFS/OS benefit with neoadjuvant EV/durva ->RC ->durva vs no peri-op Tx in cisplatin-unfit pts with MIBC! Addition of treme (anti-CTLA4) with no extra benefit @myESMO #ESMO26 #ESMOAmbassadors https://t.co/ME45RBLzF4 https://t.co/YyD9yh4qdY
��🔥 Presidential Symposium I #ESMO26 🗣️ @tompowles1 👉🏽 VOLGA phase 3, randomised, open-label trial, enrolled pts with MIBC (cT2-T4aN0/1M0 or cT1N1M0) ineligible for or refused cisplatin and were planned for RC 📌 EFS D+EV vs control: NR vs 12.1 HR 0.51 D+T+EV: NR (HR 0.61) 📌 OS D+EV vs control: 78 VS 69% at 24m HR 0.58 Triplet vs control: NS 📌 pCR Doublet vs control: 45 vs 8% 🩸ctDNA clearance impacts survival @OncoAlert @myESMO @ASCO @_SEOM @UTMDAnderson @brunolarvol 👇🏽👇🏽
𝕏Presidential symposium 1️⃣!! Volga trial: ph3 combo neoadjuvant EV + perioperative Durva +/- Treme. Dual primary endpoints of EFS were met. D+EV (HR 0.51) D+T+EV (HR 0.61) ❕#UrothelialCarcinoma #ESMO26 @myESMO @tompowles1 @FAndreMD https://t.co/HIeM2fM7L1
𝕏#ESMO26 @tompowles1 presents at the 👑presidential 👑 session VOLGA n=1009 phIII neoadjuvant #bladdercancer trial. 24mo EFS 63.5% vs 45% (HR 0.51), pCR 45% vs 10%. Triplet +tremelimumab hits EFS but not yet OS. #MIBC - @NEJM paper ➡️ ➡️ https://t.co/WlDvNeQGsc https://t.co/C8uRBpocLX
𝕏👑 This is why #Podium2Screen works! Straight from the #ESMO26 Presidential Session, @tompowles1 breaks down VOLGA for @OncoAlert: perioperative durvalumab + EV delivers major EFS and OS gains, with pCR rising to 45%. And the twist? More wasn’t necessarily better, adding tremelimumab did not improve the story. Big data + immediate context. That’s the OncoAlert advantage. 🚨
𝕏#ESMO26 VOLGA: Could just 3 cycles of neoadjuvant EV redefine treatment for cisplatin-ineligible MIBC? @tompowles1 presented landmark phase III results: 🔹 EV + durvalumab doublet: EFS HR 0.51; OS HR 0.58 (42% lower risk of death) 🔹 pCR: 45% vs 10% with surgery alone 🔹 Triplet (+ tremelimumab): EFS HR 0.61; OS not yet significant 🔹 ctDNA: ~78% positive at baseline; ~60% clearance by postsurgery assessment. 🔹 Safety: Grade 3–4 AEs ~30% with the doublet, only 11% interruption of EV 🚨The big message: Just 3 neoadjuvant cycles of EV + durvalumab, followed by cystectomy and adjuvant durvalumab alone, deliver a substantial survival benefit. A new standard for cisplatin-ineligible MIBC? 🚨Concomitant publication @NEJM @UroToday @myESMO
𝕏🔊👏Bravo Dr Thomas Powles @TomPowles1 Outstanding Presentation @ Presidential Symposium, Topline Results VOLGA Trial, Perioperative durvalumab w/ or without tremelimumab + neoadj enfortumab vedotin in muscle-invasive bladder cancer #gusm #ESMO26 @OncoAlert https://t.co/eXZW8cMZYG
𝕏VOLGA: perioperative EV + Durvalumab increases pCR, EFS and OS compared with cystectomy alone. A new standard option for these patients, in a setting that is becoming really crowded (NIAGARA, KN-905, KN-B15). #ESMO26 https://t.co/LdFwVrOXWH
𝕏Perioperative Durvalumab ± Tremelimumab Plus Neoadjuvant Enfortumab Vedotin in Muscle-Invasive Bladder Cancer: Results From the Phase 3 VOLGA Trial @OncoAlert @tompowles1 #ESMO26 https://t.co/FJ8XJ2VcZP
𝕏🇬🇧 Brilliant to see @tompowles1 AGAIN on the podium, leading the way in bladder cancer! 🚨 Phase III VOLGA: ✅ 49% ↓ EFS events/death ✅ 42% ↓ risk of death ✅ 45% pCR vs 10% Fantastic UK & @NHSBartsHealth representation! 👏 #BladderCancer #VOLGA #ESMO2026 https://t.co/82e6xXLEcU
𝕏VOLGA marks a major step forward in cisplatin-ineligible MIBC. Perioperative durvalumab plus three cycles of neoadjuvant enfortumab vedotin reduced the risk of recurrence or death by nearly 50% and improved overall survival. ctDNA clearance was associated with substantially fewer recurrences. #ESMO2026 @tompowles1
𝕏VOLGA trial : The Arm1 - in MIBC, neoadjuvant Durvalumab + EV followed by surgery then adjuvant Durvalumab showed better EFS (NR vs 12 months HR 0.51) and OS (NR in both arms, HR 0.58) compared to the standard of care. #ESMO2026 @DrChoueiri @myESMO @darioT_ @E_de_Azambuja https://t.co/BzT5qzR5uY
𝕏#ESMO26 | VOLGA in cisplatin-ineligible MIBC: Durvalumab + enfortumab vedotin significantly improved: OS: HR 0.58 (p=0.0027) EFS: HR 0.51 (p<0.0001) 2-year OS: 78% vs 69%ctDNA clearance: 60% A major advance in MIBC@SCUColombia @achoHematoYOnco @myESMO @ASCO @OncoAlert @oncodaily https://t.co/Y1hvotHtif
𝕏ESMO 2026 - presidential LBA | VOLGA Phase III – Perioperative Durvalumab + Enfortumab Vedotin (EV) in cisplatin-ineligible/refusing patients: 📊 EV + Durva vs Control • 2-year EFS: 64% vs 45% (HR 0.51; p<0.0001) • 2-year OS: 78% vs 69% (HR 0.58; p=0.0027) • pCR: 45% vs 10% Adding tremelimumab improved EFS (HR 0.61) but no significant OS benefit yet, with higher grade 3/4 toxicity (42% vs 30%). 🔥can this stop the need of post op EV ? Probably yes . New SOC 🙂👍 Looking forward the full datasets @OncBrothers @OncoAlert @myESMO #ESMO26 #VOLGA #BladderCancer
𝕏#ESMO26 | VOLGA | Presidential Symposium-1 In cisplatin-ineligible/refusing MIBC, neoadjuvant EV + perioperative durvalumab significantly improved EFS and OS vs the control arm. EFS: HR 0.55 (24-month: 78% vs 69%) OS: HR 0.58 (24-month: 83% vs 75%) pCR: 45% vs 10% Impressive results! Unlike KEYNOTE-905/EV-303, EV was administered only in the neoadjuvant setting, with no adjuvant EV. I’m looking forward to the discussion during the session.
𝕏VOLGA (LBA2): perioperative durva ± tremelimumab + neoadjuvant EV vs cystectomy control in cisplatin-ineligible/refusing MIBC. 24-mo EFS 64% vs 45% with durva + EV, HR 0.51 (95% CI 0.38-0.67); 60% vs 45% with the triplet, HR 0.61 (95% CI 0.47-0.80). No trimodality arm. This doesn't answer the bladder-preservation comparison. #ESMO26 #radonc https://t.co/3skudJjr5t
𝕏🚨 What a great start to #ESMO2026! 🇪🇺 The European Commission approves perioperative enfortumab vedotin + pembrolizumab for resectable MIBC, regardless of cisplatin eligibility! A major milestone for our patients. Now looking forward to VOLGA at the Presidential Symposium on Saturday! @tompowles1 With only 3 neoadjuvant EV cycles and no adjuvant EV, VOLGA could provide important insights into a key question: How much EV do we really need? Does adjuvant EV add meaningful efficacy—or mainly cumulative toxicity? Cross-trial comparisons cannot answer this definitively. Biomarker-guided de-escalation trials are urgently needed! 🔬 @DrChoueiri @Markuseckstein3 @DrRosenbergMSK @Dr_Aggen @tompowles1 @urotoday @UroDocAsh @Uromigos @weoncologists @OncoAlert @raffcolo @PTarantinoMD @drenriquegrande @DrYukselUrun @AndreaNecchi @apolo_andrea
𝕏🌊 VOLGA | ESMO 2026 A River by Name. A New Course in Bladder Cancer Treatment? Named after the Volga River — Europe's longest river, flowing through Russia into the Caspian Sea. Cisplatin-Free. Adjuvant EV-Free. The Phase III VOLGA trial (N = 695) evaluated perioperative durvalumab ± tremelimumab with neoadjuvant enfortumab vedotin in cisplatin-ineligible or cisplatin-declining MIBC. 🔹 EV + durvalumab: Significant EFS and OS benefit versus surgery-based control. 🔹 Adding tremelimumab: EFS benefit reported; OS not statistically significant at interim analysis. 🔹 Key distinction: EV is given ONLY before surgery — no adjuvant EV! 🔹 FDA: Priority Review granted; decision expected Q4 2026. The big question: Can shorter EV exposure deliver durable survival benefit with less treatment burden? Full results awaited at ESMO on 24 October 2026. 📚 Reference: Powles TB et al. VOLGA Phase III trial. ESMO 2026; LBA2. NCT04960709. AstraZeneca, September 2026. #ESMO26 #VOLGA #BladderCancer #MIBC #EnfortumabVedotin #Durvalumab #UroOncology #MVOnco
𝕏VOLGA tests a key perioperative strategy in cisplatin-ineligible or cisplatin-declining MIBC. EV + durvalumab improved EFS and OS; adding tremelimumab met EFS, but OS was not significant at interim analysis. Now the key question: magnitude of benefit vs toxicity. Presented by @tompowles1 @myESMO #ESMO26 #BladderCancer
𝕏I’d applaud these trials, but I’d remain seated 😅😅 INTerpath-001 is an innovative treatment approach. However, there is no comparison with neoadjuvant nivo + ipi, a strong option particularly in macroscopic stage III melanoma. DeLLphi-305 showed a survival benefit with maintenance tarlatamab + durvalumab. But the comparator is durvalumab monotherapy. We also have positive results from IMforte with maintenance atezo + lurbinectedin. So this is another potential maintenance option; its place among the existing options remains to be defined. In HARMONi-GI1, even if not one but three trucks could fit between the Kaplan–Meier curves, global validation will still be expected because the trial was conducted exclusively in China 🫣 For me, VOLGA’s most interesting feature is the omission of adjuvant EV. As for the survival benefit of perioperative EV + immunotherapy, we already have strong data.
𝕏As an oncologist, this is the list I’d want in front of me before walking into the GU sessions. My personal must-watch is VOLGA. If EV plus durvalumab ± tremelimumab delivers in cisplatin-ineligible MIBC, it changes the conversation for many of our patients. I’m also keen to see CAPItello-281’s overall survival, since it’s a real test for biomarker-driven therapy in mHSPC. Thank you to our senior faculty and faculty for curating this! #WeAreOncoAlert #ESMO26
Both experimental arms met the EFS primary endpoint. Perioperative Imfinzi + neoadjuvant EV (Arm 2) demonstrated a statistically significant and clinically meaningful improvement in EFS versus standard of care. Perioperative Imfinzi + Imjudo + neoadjuvant EV (Arm 1) also demonstrated a statistically significant and clinically meaningful improvement in EFS versus standard of care. By blinded independent central review (ITT; data cut-off 2 March 2026; median follow-up 23 months): durvalumab + EV (n=233) vs control (n=229) — 84 (36%) vs 123 (54%) events; median EFS not reached (33.2–NC) vs 12.1 months (7.6–27.0); HR 0.51 (95% CI 0.38–0.67); stratified log-rank P<0.0001 (boundary 0.0218); 12/24-month EFS 73%/64% vs 50%/45%. Durvalumab + tremelimumab + EV (n=233) vs control — 92 (39%) vs 123 (54%) events; median not reached (27.9–NC) vs 12.1 months; HR 0.61 (0.47–0.80); P=0.0004 (boundary 0.0270); 12/24-month EFS 67%/60% vs 50%/45%. Topline (14 May 2026): AstraZeneca announced both arms met EFS without effect sizes.
EFS HR 0.51 (D+EV) · HR 0.61 (D+T+EV) vs controlPerioperative Imfinzi + neoadjuvant EV (Arm 2) demonstrated a statistically significant and clinically meaningful improvement in overall survival versus standard of care. The triplet arm (Arm 1: Imfinzi + Imjudo + EV) showed a favourable trend for OS but did not reach statistical significance at this planned interim analysis; OS for the triplet will be formally reassessed at a subsequent analysis. At the ESMO 2026 presentation (ITT; data cut-off 2 March 2026; median follow-up 26 months): durvalumab + EV vs control — 49 (21%) vs 74 (32%) deaths; median OS not reached in either arm; HR 0.58 (95% CI 0.40–0.83); stratified log-rank P=0.0027 (boundary 0.0104); 12/24-month OS 87%/78% vs 81%/69%. Durvalumab + tremelimumab + EV vs control — 60 (26%) vs 74 (32%) deaths; HR 0.77 (0.54–1.07); P=0.1230 (boundary 0.0138); not statistically significant; follow-up ongoing.
OS HR 0.58 (D+EV, significant) · HR 0.77 (D+T+EV, not significant)Durvalumab + EV vs control (ITT; patients without surgery or with a missing/non-evaluable assessment counted as non-responders): 45% (105/233; 95% CI 38.6–51.7) vs 10% (22/229; 6.1–14.2) by local pathology review, risk ratio 4.7 (3.1–7.3); 40% (94/233) vs 8% (19/229) by central independent review, risk ratio 4.8 (3.1–7.9) (data cut-off 2 March 2026).
pCR 45% vs 10% (local review)Per AstraZeneca, the safety and tolerability of Imfinzi with or without Imjudo plus EV was consistent with the known safety profiles of the individual medicines, with no new safety signals identified at this interim analysis. Presented safety data (overall trial period; safety population D+EV n=228, D+T+EV n=229, control n=229; data cut-off 2 March 2026): maximum grade 3–4 AEs of any cause 64% / 70% / 44%; serious AEs 63% / 70% / 44%; AEs leading to death 7% / 9% / 6%; treatment-related AEs leading to death 0.4% / 2%; AEs leading to discontinuation of any study treatment 21% / 31% (EV discontinuation 11% / 23%); AEs leading to cancellation of surgery 0.9% / 3% / 0; grade 3–4 immune-mediated AEs 11% / 20% / 0.9%.
Grade 3–4 AEs 64% (D+EV) / 70% (D+T+EV) / 44% (control)Regulatory status & clinical implications - Investigational - not FDA approved. Positive Phase 3 topline reported May 14, 2026; FDA granted Priority Review to the durvalumab + enfortumab vedotin doublet on September 25, 2026 (PDUFA date Q4 2026). If validated by detailed data and regulatory review, VOLGA would establish a chemo-free perioperative immunotherapy + ADC backbone for cisplatin-ineligible MIBC — a population historically with limited curative-intent options beyond cystectomy. Doublet durvalumab + EV (Arm 2) emerged as the cleaner regimen at interim, achieving both EFS and OS. The triplet's incremental contribution beyond doublet remains an open question pending mature OS and detailed subgroup data.
Presented - Full VOLGA data were presented at the ESMO 2026 Presidential Symposium (LBA2), Saturday, October 24, 2026 (Madrid), by Prof. Thomas Powles. ESMO 2026 LBA2 slides · LBA2 triplet + safety slides
Sponsor / drugs - AstraZeneca; durvalumab (Imfinzi) + enfortumab vedotin (Padcev) +/- tremelimumab (Imjudo).
Compiled and reviewed by the KOL Pulse research team, led by Brian Shields, Founder, KOL Pulse. Last updated October 26, 2026.
| Arm | N | Events, n (%) | Median, mo (95% CI) | 12 months rate | 24 months rate |
|---|---|---|---|---|---|
| Durvalumab+EV | 233 | 84 (36) | NR (33.2–NC) | 73% | 64% |
| Control | 229 | 123 (54) | 12.1 (7.6–27.0) | 50% | 45% |
| Arm | N | Events, n (%) | Median, mo (95% CI) | 12 months rate | 24 months rate |
|---|---|---|---|---|---|
| Durvalumab+EV | 233 | 49 (21) | NR (NC–NC) | 87% | 78% |
| Control | 229 | 74 (32) | NR (37.7–NC) | 81% | 69% |
| Arm | N | Events, n (%) | Median, mo (95% CI) | 12 mo rate | 24 mo rate |
|---|---|---|---|---|---|
| D+T+EV | 233 | 92 (39) | NR (27.9–NC) | 67% | 60% |
| Control | 229 | 123 (54) | 12.1 (7.6–27.0) | 50% | 45% |
| Arm | N | Events, n (%) | Median, mo (95% CI) | 12 mo rate | 24 mo rate |
|---|---|---|---|---|---|
| D+T+EV | 233 | 60 (26) | NR (NC–NC) | 82% | 75% |
| Control | 229 | 74 (32) | NR (37.7–NC) | 81% | 69% |
| Arm | N | 12 mo rate | 24 mo rate |
|---|---|---|---|
| Persistent negative | 24 | 91% | 91% |
| Clearance | 52 | 88% | 81% |
| Persistent positive | 35 | 70% | 55% |
| Arm | N | Events, n (%) | Median, mo (95% CI) | 12 months rate | 24 months rate |
|---|---|---|---|---|---|
| EV + pembro | 170 | 48 (28.2) | NR (37.3–NR) | 77.8% | 74.7% |
| Control | 174 | 95 (54.6) | 15.7 (10.3–20.5) | 55.1% | 39.4% |
| Arm | N | Events, n (%) | Median, mo (95% CI) | 12 months rate | 24 months rate |
|---|---|---|---|---|---|
| EV + pembro | 170 | 38 (22.4) | NR (NR–NR) | 86.3% | 79.7% |
| Control | 174 | 68 (39.1) | 41.7 (31.8–NR) | 75.7% | 63.1% |
VOLGA (NCT04960709) is a Phase III, randomized, open-label, multi-centre global trial sponsored by AstraZeneca evaluating perioperative durvalumab (Imfinzi) with or without tremelimumab (Imjudo) in combination with neoadjuvant enfortumab vedotin (EV) versus radical cystectomy with or without approved adjuvant therapy in patients with muscle-invasive bladder cancer (MIBC) who are ineligible for or have declined cisplatin-based chemotherapy. The trial enrolled 695 patients across 182 centres in 25 countries and was designed with dual primary EFS endpoints for each experimental arm versus the standard-of-care comparator.
Results are in At a Glance.
Adults with muscle-invasive urothelial carcinoma of the bladder undergoing radical cystectomy who were ineligible for or had declined cisplatin-based chemotherapy.
Phase 3, randomised, open-label, multi-centre. 695 patients randomised 1:1:1 across 182 centres in 25 countries (Europe, North America, South America, Asia).
3 cycles Imfinzi + EV plus 2 cycles Imjudo (neoadjuvant) → radical cystectomy → 9 cycles Imfinzi + 1 cycle Imjudo (adjuvant).
3 cycles Imfinzi + EV (neoadjuvant) → radical cystectomy → 9 cycles Imfinzi adjuvant monotherapy.
Radical cystectomy with or without approved adjuvant therapy (standard of care).
Dual primary endpoints of EFS for Arm 1 vs Arm 3 and Arm 2 vs Arm 3.
Key secondary: overall survival (D+EV vs control; D+T+EV vs control). Other secondary: pCR, EORTC QLQ-C30; exploratory: ctDNA (ESMO 2026 LBA2 design slide). ClinicalTrials.gov also lists DFS, pathologic downstaging, disease-specific and metastasis-free survival.
AstraZeneca. NCT04960709 / EudraCT 2020-005452-38 / D910PC00001.
VOLGA (NCT04960709) is an AstraZeneca Phase 3 randomized trial in 695 patients with cisplatin-ineligible muscle-invasive bladder cancer, testing perioperative durvalumab (Imfinzi) plus neoadjuvant enfortumab vedotin, with or without tremelimumab (Imjudo), versus standard of care. Event-free survival is the dual primary endpoint. See Trial Design.
Both experimental arms met the event-free survival primary endpoint. Durvalumab + EV also improved overall survival at the interim analysis (EFS HR 0.51, OS HR 0.58; ESMO 2026 LBA2); the triplet’s OS was not statistically significant. Figures, sources and data cut-off: At a Glance.
Not yet. The durvalumab + enfortumab vedotin regimen is investigational; on September 25, 2026 the FDA granted Priority Review to AstraZeneca’s supplemental application, with a PDUFA date in Q4 2026. See At a Glance.
VOLGA gives 3 neoadjuvant cycles of EV, with no further EV after surgery; durvalumab (± tremelimumab) continues alone in the adjuvant phase. EV-303 continues EV into the adjuvant phase, and several physicians on this page flag VOLGA’s shorter EV course as a possible tolerability advantage because EV toxicity is cumulative. Dosing: Trial Design.
Cisplatin-ineligible MIBC has had limited curative-intent options beyond cystectomy. VOLGA tests a chemotherapy-free perioperative immunotherapy-plus-ADC approach; the doublet arm met both event-free and overall survival. See At a Glance.
Per AstraZeneca, safety was consistent with the known profiles of the individual medicines, with no new safety signals. Grade 3–4 adverse event rates, deaths and discontinuations by arm are in At a Glance.
FDA accepted and granted Priority Review to the sBLA for durvalumab + enfortumab vedotin (doublet arm only) in cisplatin-ineligible MIBC, based on the VOLGA interim EFS and OS results. PDUFA date in Q4 2026.
Topline results: Arm 2 (Imfinzi + EV) hit stat-sig EFS and OS. Arm 1 (Imfinzi + Imjudo + EV) hit EFS with a favourable but non-significant OS trend at this interim. No new safety signals.
Original AstraZeneca corporate announcement. Quotes from Thomas Powles (international coordinating investigator) and Susan Galbraith (EVP, Oncology R&D). Positions VOLGA alongside NIAGARA and POTOMAC.
Correction summary clarifying the three-arm design and the differential results for Arm 1 vs Arm 2. Useful side-by-side framing of which arm hit which endpoint.
Investor-oriented context on MIBC epidemiology: ~25% of bladder cancer patients have muscle-invasive disease, and up to 50% of those are cisplatin-ineligible. Frames the commercial setting around radical cystectomy.
UK regulatory news service version of the AstraZeneca announcement, including the planned regulatory submission language: "shared with global regulatory authorities."
Authoritative protocol record: 3-arm design, 695 patients randomised, dual primary EFS endpoints, key secondary endpoints (OS, pCR, DFS, pathologic downstaging), and full inclusion/exclusion criteria.
