Physician discussion of GU trials, October 23–25
Physician posts on X, October 23–25.
The eleven most-discussed trials are covered below.
Bladder cancer
VOLGA: durvalumab + 3 cycles of neoadjuvant EV, cisplatin-ineligible MIBC
Phase 3, N=695, cisplatin-ineligible or refusing. Durvalumab + EV vs control: EFS HR 0.51 (95% CI 0.38–0.67), 24-month EFS 64% vs 45%. OS HR 0.58 (0.40–0.83), 24-month OS 78% vs 69%. pCR 45% vs 10% (local review). The triplet arm with tremelimumab: EFS HR 0.61 (0.47–0.80); OS HR 0.77 (0.54–1.07), not significant. Grade 3–4 AEs of any cause 64% (durvalumab + EV), 70% (triplet), 44% (control). (ESMO 2026 LBA2, Tom Powles; data cutoff Mar 2, 2026) Investigational. FDA granted Priority Review to durvalumab + EV on September 25, 2026. (KOL Pulse VOLGA page)
VOLGA event-free survival, durvalumab + EV vs control. Tom Powles, ESMO 2026 Presidential Symposium, LBA2. Photo posted by
@shilpaonc.
Physicians favored the doublet. The debate was the triplet’s added toxicity and how much EV is needed, since VOLGA gave no adjuvant EV.
Presenter first, then agreement and debate
VOLGA 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.
View post on X ↗
Kudos @tompowles1 on a fantastic #VOLGA presidential @ #ESMO26 👏
Less is More!
• Cis-inelig MIBC, 25% were cis refusers
• D+EV x3 → RC → adj D x9 (NO adj EV)
• EFS HR 0.51
• OS HR 0.58
• pCR 45 vs 10%
• G3-4 TRAE 30%,
• neuropathy only 18%
• imAEs 33% (G3-4 11%)
• GHS/QoL maintained post-RC
• Treme ↑tox (G3-4 42%, 5 deaths), NO OS gain.
My take: it's not just about chasing bigger numbers. Tox matters too, especially when OS is achieved. Need to discuss the pros and cons with patients.
Less PN and skin tox, and fewer G3+ immune AEs than more cycles and that's a win for patients ! 🙌
@Uromigos @OncoAlert @brian_rini @LosUromigos @drenriquegrande
View post on X ↗
💫#VOLGA: Durva + EV in cis-ineligible, like #EV303 but NO adjuvant EV here
⬆️ 2-year EFS (HR 0.51), OS (HR 0.58) & pCR (45% vs 10%)
Triplet arm OS not significant & ⬆️ tox
Less robust #s then EVP but how much benefit does adjuvant EV add? Can we use ctDNA/pCR to ⬇️? #ESMO26
https://t.co/UruMRqJPnI KEYNOTE-866 and ENERGIZE: two negative Phase 3 trials of PD-1 + cisplatin chemotherapy
Both trials added a PD-1 inhibitor to neoadjuvant gemcitabine-cisplatin, continued after cystectomy, in cisplatin-eligible MIBC. KEYNOTE-866 (pembrolizumab, N=907): EFS HR 0.88 (95% CI 0.71–1.10), one-sided P=0.1366, not significant. OS HR 1.00 (0.79–1.27). pCR 44.4% vs 35.8%; OS and pCR were not formally tested. (ESMO 2026 4735O, Jens Bedke; data cutoff Jan 26, 2026) ENERGIZE (nivolumab, N=653): EFS HR 0.94 (0.72–1.24), P=0.6697. pCR 39.1% vs 29.6%, not significant after multiplicity adjustment. Both co-primary endpoints were missed. (ESMO 2026 4736O, Andrea Necchi; median follow-up 54.5 months) Neither regimen is approved for MIBC. NIAGARA, with durvalumab on the same chemotherapy backbone, was positive.
KEYNOTE-866 event-free survival. Jens Bedke, ESMO 2026 proffered paper session, 4735O. Photo posted by
@katy_beckermann.
Physicians noted that higher pCR did not translate into EFS. Explanations offered for the difference from NIAGARA included control-arm outcomes, trial populations and the need for biomarker selection.
Why NIAGARA and not these two?
Bravo @AndreaNecchi on a superb presentation of ENERGIZE trial at @myESMO #ESMO26 ! 👏
Ph3, n=653 cis-eligible MIBC: neoadj GC + nivo → adj nivo vs GC alone.
Median f/u 54.5 mo.
🔹 pCR 39.1% vs 29.6%: not dig
🔹 EFS HR 0.94: co-primaries not met
🔹 OS HR 0.88
👉Negative trial, but the ctDNA data are a key message: detectable ctDNA at baseline and after NAC strongly prognostic for worse EFS & OS.
Selecting patients by ctDNA, rather than adding IO for all, is where the field is heading!
Great to see this build on our Ph2 BLASST-1. Despite the negative result, it's very practice-informing.
Proud to be a part of this effort!
@CleClinicMD @caseccc @CleClinicUro @sonpavde @MattGalsky @MichvdHeijden @Uromigos @Annals_Oncology @tompowles1
View post on X ↗
Negative Ph.III KEYNOTE-866 by #DrJensBedke: perioperative pembrolizumab + neoadjuvant Gem/Cis vs placebo + Gem/Cis in cis-eligible MIBC.
EFS HR 0.88 (95% CI 0.71-1.10), p=0.137.
pCR 44.4% vs 35.8%; OS HR 1.00.
Higher pCR did not translate into EFS benefit.
#ESMO26 #BladderCancer @myESMO @OncoAlert
View post on X ↗
Nice comparison chart @tompowles1 — control cohorts in the #ENERGYZE & #Keynote866 trials both did much better than #NIAGARA control cohort… some may have had access to adjuvant IO to contribute to EFS?
#ESMO26 @myESMO @OncoAlert
https://t.co/K6ubio90xc
ENERGIZE: Another negative perioperative IO trial in MIBC.
Nivo + GC → cystectomy → nivo failed to improve EFS (HR 0.94, p=0.67). OS HR 0.88.
Notably, split-dose cisplatin was allowed and 77% had cT2 disease. Again, excellent outcomes in the control arm.
#ESMO26 @OncoAlert
https://t.co/9g4zjz7Nq7 KEYNOTE-B15 / EV-304: ctDNA from the approved perioperative EV + pembrolizumab regimen
Exploratory ctDNA analysis (Signatera) presented by Jonathan Chatzkel. ctDNA clearance from baseline to surgery 82.1% vs 66.7% with EV + pembrolizumab vs gemcitabine-cisplatin. ctDNA-positive after surgery 4.8% vs 13.5%. pCR 72.4% vs 43.7% in patients ctDNA-negative before surgery, and 3.7% vs 2.2% in those still ctDNA-positive. ctDNA-positive status was associated with worse EFS in both arms. (ESMO 2026 Abstract 4734O and slides; discussant slide for pCR by ctDNA; data cutoff Oct 27, 2025) ctDNA is not validated to guide treatment. Perioperative EV + pembrolizumab has been FDA approved for MIBC since July 10, 2026, based on the trial’s EFS and OS results. (KOL Pulse KEYNOTE-B15 page)
KEYNOTE-B15 ctDNA clearance and EFS. Jonathan Chatzkel, ESMO 2026, 4734O. Photo posted by
@tompowles1.
Physicians agreed ctDNA is prognostic. The open question is whether ctDNA and pCR can guide de-escalation, including adjuvant EV and bladder sparing.
Prognostic now; de-escalation later?
ctDNA analysis from the EVP vs chemotherapy muscle invasive bladder cancer trial (B15/EV304) shows ctDNA is strongly prognostic at all time points for both arms. EVP has higher clearance rates across time points, underlining its ⬆️ activity. Results for the control arm are strikingly similar to the ctDNA results in the chemo control arm in the NIAGARA trial. This consistency underlines the utility of ctDNA from a prognostic perspective.#ESMO26 @OncoAlert
View post on X ↗
KEYNOTE-B15 ctDNA analysis presented by Jonathan Chatzkel at #ESMO26, with Min Teo as discussant 🧬 In cisplatin-eligible MIBC, ctDNA+ before surgery meant almost no pCR with either regimen (3.7% with EV + pembro, 2.2% with cis/gem). Among ctDNA− patients, pCR was 72.4% with EV + pembro vs 43.7% with cis/gem. In the EV + pembro arm, patients who cleared ctDNA had 24-month EFS of 81% vs 33% with persistent ctDNA+. The postsurgery results replicate NIAGARA. Serial ctDNA could open the door to bladder-sparing and surveillance questions. #MRD #ctDNA #BladderCancer
View post on X ↗
🚨 Important new ctDNA data from KEYNOTE-B15 at ESMO 2026!
In cisplatin-eligible MIBC, EV+pembrolizumab achieved:
🔹 82.1% ctDNA clearance during neoadjuvant treatment vs 66.7% with gemcitabine/cisplatin.
🔹 87.0% ctDNA negativity before surgery vs 80.3% with chemotherapy.
🔹 95.2% ctDNA negativity after cystectomy vs 86.5% with chemotherapy.
Strikingly, only 4.8% remained ctDNA-positive after neoadjuvant EV+pembrolizumab and surgery!
We know from IMvigor011 that postoperative ctDNA can identify patients at high risk of recurrence and help guide adjuvant treatment strategies.
But what about patients achieving both pCR and sustained ctDNA negativity?
Do they really need another 5–6 cycles of adjuvant EV, with the potential for cumulative tox/ neuropathy?
Could pCR + ctDNA clearance, followed by longitudinal ctDNA monitoring, define a population suitable for treatment de-escalation?
VOLGA will add another important piece to this puzzle, using only 3 neoadjuvant EV cycles without adjuvant EV.
Of course, neither KEYNOTE-B15 nor VOLGA can establish the necessity of adjuvant EV through cross-trial comparisons.
We urgently need prospective, biomarker-guided de-escalation trials—not simply more treatment for everyone.
@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
View post on X ↗ KEYNOTE-905 / EV-303: what pembrolizumab alone adds, in an ad hoc three-arm analysis
Ad hoc analysis of 255 cisplatin-ineligible or cisplatin-declining patients randomized concurrently to EV + pembrolizumab (n=85), pembrolizumab alone (n=83) or cystectomy alone (n=87). 24-month EFS 75.8%, 55.8% and 41.0%. EFS HR vs cystectomy alone 0.40 (95% CI 0.25–0.65) for EV + pembrolizumab and 0.71 (0.47–1.07) for pembrolizumab alone. OS HR 0.48 (0.29–0.80) and 0.76 (0.48–1.20). pCR 58.8%, 25.3% and 10.3%. All comparisons were descriptive, not prespecified hypothesis tests. (ESMO 2026 4733O slides, Anders Ullén; data cutoff Jun 6, 2025) Perioperative EV + pembrolizumab has been FDA approved since November 21, 2025, based on the primary two-arm analysis. Perioperative pembrolizumab alone is not approved for MIBC. (KOL Pulse KEYNOTE-905 page)
KEYNOTE-905 event-free survival, ad hoc three-arm analysis. Anders Ullén, ESMO 2026, 4733O. Photo posted by
@tompowles1.
Physicians read the result as support for both drugs. The questions were which patients need EV on top of pembrolizumab, and how much toxicity the added EV brings.
Both drugs contribute; who needs both?
Perioperative EV + Pembro momentum by #DrAndersUllen in KEYNOTE-905 Ph.III ad hoc analysis of cis-ineligible MIBC.
2-yr EFS: 75.8% EV/Pembro vs 55.8% Pembro vs 41.0% surgery alone.
EFS HR 0.40 vs 0.71 (each vs control).
pCR 58.8% vs 25.3% vs 10.3%.
#ESMO26 #BladderCancer @myESMO @OncoAlert
View post on X ↗
The ad hoc analysis, 255 concurrently randomised, cisplatin-ineligible:
[...]
2️⃣ 41% of patients on EV+P still have residual disease. We will not find them just with a IHC cutoff.
[...]
Also worth stating plainly: this is an ad hoc comparison, not a powered head-to-head. Pembro alone did not separate from surgery here (CI crosses 1). Interpret the three-arm ranking accordingly.
Read the full post on X ↗
KEYNOTE-905: pembro alone raises a question worth testing. Who might safely need less?
@myESMO @FAndreMD @curijoey @DrChoueiri @OncoAlert @OpenMedicineHQ #ESMO26 @Uromigos
https://t.co/Qplp3Osdrc
Free Access · KOL Pulse Intelligence
Track oncology’s top KOLs in your specialty
Create a free account, pick the tumor types you cover, and go beyond the tweet — the intelligence pharma teams use to map influence and prepare for engagement:
- ✓Enhanced KOL profiles
- ✓Pharma influence & potential advisory-board patterns
- ✓2025 Open Payments financial analysis
- ✓Social-media sentiment & trend signals
Get free access — pick your specialty
Choose the tumor types you follow. No cost, unsubscribe anytime.
Kidney cancer
XmAb819: an ENPP3 × CD3 T-cell engager in heavily pretreated clear cell RCC
Phase 1 study (XmAb819-01, NCT05433142) of XmAb819, a bispecific T-cell engager that targets ENPP3, in patients with relapsed or refractory clear cell RCC after a checkpoint inhibitor and a VEGFR TKI. Sumanta K. Pal of City of Hope presented the data in the October 25 GU proffered paper session, and Manuela Schmidinger discussed it. XmAb819 is investigational. Source: XmAb819 presentation, ESMO 2026 program.
XmAb819-01 study design. Sumanta K. Pal, ESMO 2026, GU proffered paper session. Photo posted by
@DrDanielHeng.
Physicians, including the LITESPARK-011 presenter, called the activity promising in heavily pretreated disease and pointed to ENPP3 as a new target in RCC. The caveat they raised: these are Phase 1 data, and randomized trials are needed. Pal’s own posts, quoted below, are on LITESPARK-011 and LITESPARK-012.
Discussant’s session first, then reactions
Emerging RCC immunotherapy strategies intricately discussed by @schmidingerRCC: ENPP3×CD3 T-cell engagement with XmAb819 in heavily pretreated ccRCC and dual PD-1/VEGF targeting with ivonescimab in 1L favorable-risk disease.
Promising signals; randomized validation remains key.
#RCC @myESMO #ESMO26 @OncoAlert
View post on X ↗
XmAb819 shows impressive activity in mRCC from a phase I trial. Great job @montypal and team! @OncoAlert #ESMO26
https://t.co/OUIVwDaeLG
@montypal w phase 1 data from XmAb819 ENPP3/CD3 bispecific in tx-refractory #kidneycancer — manageable CRS & promising responses dose dependent. ENPP3 very interesting target for RCC.
@oncoalert #ESMO26 @myESMO
https://t.co/Yur2ZjCBct
Exciting to see novel immune-engaging strategies in RCC. XmAb819, ENPP3×CD3 bispecific T-cell engager, showed activity in heavily pretreated ccRCC, highlighting potential of ENPP3 as a therapeutic target beyond VEGF, IO, HIF-2α pathways. #ESMO2026 @montypal @cityofhope @OncoAlert
https://t.co/YZ5fd0BXhK LITESPARK-011 final analysis: belzutifan + lenvatinib vs cabozantinib after PD-1/PD-L1 therapy
Phase 3, N=747, presented by Daniel Heng (3587O) and published at the same time in Annals of Oncology. Overall survival, a dual primary endpoint, was not statistically significant: median 33.7 vs 28.6 months, HR 0.85 (95% CI 0.70–1.03), one-sided P=0.04689 against a prespecified boundary of 0.0223. PFS by blinded central review: median 14.8 vs 10.8 months, HR 0.74 (0.62–0.88), not formally re-tested at this analysis. ORR 53.1% vs 40.2%; median duration of response 22.0 vs 11.9 months. Grade 3 or higher adverse events 85.4% vs 83.0%. (ESMO 2026 3587O / Annals of Oncology, final analysis; data cutoff Feb 2, 2026) PFS was statistically significant at the first interim analysis: median 14.6 vs 10.6 months, HR 0.74 (0.61–0.89), one-sided p=0.00095. (FDA label; first interim analysis (IA1), data cutoff Jun 26, 2024) The FDA approved belzutifan + lenvatinib on September 24, 2026 for adults with advanced RCC with a clear cell component after a PD-1 or PD-L1 inhibitor, based on PFS and ORR. No overall survival benefit has been demonstrated. (KOL Pulse LITESPARK-011 page)
LITESPARK-011 final overall survival. Daniel Heng, ESMO 2026, 3587O. Photo posted by
@DrChoueiri.
Physicians agreed the PFS and response benefit held up and that OS missed significance. The debate was whether the combination should displace single-agent therapy after immunotherapy, given lenvatinib tolerability and cardiac toxicity.
The result, then the treatment choice
Post-IO RCC update by @DrDanielHeng in LITESPARK-011 Ph.III:
Bel/Len vs Cabo maintained PFS benefit (14.8 vs 10.8 mo; HR 0.74).
ORR 53% vs 40%; DOR 22 vs 12 mo.
OS favored Bel/Len (33.7 vs 28.6 mo; HR 0.85) but missed significance boundary.
#ESMO26 #RCC @myESMO @OncoAlert
https://t.co/WMYWwaAPYD
Great presentation by @DrDanielHeng at #ESMO26 on #LITESPARK11. Congrats on simultaneous publication of the data in @Annals_Oncology! It’s a high bar to advance therapies in the 2nd line setting. I tend to still favor monotherapy for most - have had challenges with Len 20 & also want to understand more about the cardiac tox. Still, always eager to have more options to discuss with my patients! @OncoAlert
View post on X ↗
LITESPARK-011: Len-Bel improves ORR and PFS compared with Cabo in IO-pretreated mRCC, but without a statistically significant improvement in OS. Are these results good enough to establish Len-Bel as a standard therapy in this setting over Cabo monotherapy? #ESMO26
https://t.co/YppMriTnXu LITESPARK-012: adding belzutifan or CTLA-4 blockade to first-line pembrolizumab + lenvatinib
Phase 3, three arms, in previously untreated advanced clear cell RCC: pembrolizumab + lenvatinib with belzutifan, or with quavonlimab (an anti-CTLA-4 antibody) coformulated with pembrolizumab, vs pembrolizumab + lenvatinib. Toni Choueiri presented the trial (3586O), with a concurrent publication in Annals of Oncology. Neither triplet improved PFS or OS over pembrolizumab + lenvatinib, and more patients stopped treatment because of adverse events on the triplets. Both triplets are investigational; pembrolizumab + lenvatinib, the control arm, is an FDA-approved first-line regimen. Source: 3586O abstract, ESMO 2026 program.
LITESPARK-012 PFS, belzutifan triplet vs pembrolizumab + lenvatinib. Toni Choueiri, ESMO 2026, 3586O. Photo posted by
@DrChoueiri.
Physicians read the trial as a limit on stacking current drug classes. Explanations offered included toxicity reducing the dose intensity of the doublet and a strong control arm; others asked which patients, if any, need CTLA-4 blockade.
Presenter first, then what it means
More is not always better in 1L RCC! Presenting LITESPARK-012 Ph.III: adding belzutifan or CTLA-4 blockade to Pembro/Len failed to improve PFS or OS.
Read the full post on X ↗
Interesting data from @DrChoueiri @DanaFarber from #LITESPARK12. Seems as though we have reached the max in what we can do with combining current classes of tx frontline. Need to see if we can incorporate novel tx upfront! #ESMO26 @brian_rini @tompowles1 @AlbigesL @OncoAlert
https://t.co/KGNrgz1wcF
LITESPARK-12 tested Len/pem/bel (VEGF/PD1/HIF) vs Len/pem in 1st line RCC #ESMO26 (supported by a RII +ve PFS R2 @AlbigesL @crisuarez08). In the R3 both PFS and OS hasd HRs~1 with ⬆️ tox for triplets. Belzutifan doublets seem active so why do the triplets fail. It’s likely due to the increased toxic compromising dose intensity of the extremely active Len/pem (2 yr PFS). There seems a limit to tolerable drug intensity- triplets (COSMIC313 too) maybe a step too far. @OncoAlert @DrChoueiri
View post on X ↗
Proud to have contributed to LITESPARK-012.
A reminder that adding more drugs does not always mean better outcomes. Negative trials help us protect patients from unnecessary toxicity.
@myESMO @OncoAlert @OpenMedicineHQ #ESMO26 @Annals_Oncology @tompowles1 @DrChoueiri @curijoey @AnkaraUni @Ankaratip1945
View post on X ↗ Prostate cancer
DASL-HiCaP: darolutamide added to ADT and radiation in very high-risk localized prostate cancer
Phase 3, placebo-controlled trial (ANZUP1801) presented by Tamim Niazi in Presidential Symposium I (LBA4), with Silke Gillessen as discussant. The presented result was an interim analysis; the trial reported a metastasis-free survival benefit with darolutamide. Darolutamide is investigational in this setting. Source: LBA4 abstract, ESMO 2026 program.
DASL-HiCaP primary endpoint. Tamim Niazi, ESMO 2026 Presidential Symposium I, LBA4. Photo posted by
@alantanmd.
The US lead investigator called it a new standard of care. Others focused on patient selection, nodal disease and what the abstract did not report about radiation.
Standard of care, or for whom?
1/n Major congrats to our DASL team, especially to @ChrisSweens1 and @niazi_Dr7, and a big thanks to the patients. Working with @ANZUPtrials and @ThePCCTC on DASL as US lead has been a career highlight.
I'd contend this establishes a new standard of care in DASL very-high risk PCa. The conventional-image defined MFS benefit with the addition of Darolutamide to RT+ADT was extraordinarily robust; the DSMC recommended reporting out at IA. #ESMO26, #radonc, #medtwitter. @MSKCancerCenter @MSK_RadOnc. #pcsm
Brief 🧵
View post on X ↗
Rather a brilliant discussion at the presidential #ESMO26 for the DASL very high risk prostate cancer trial
The future is patient selection. The clearest indication is in pateints with N1 disease supported by results from thr other trials @OncoAlert @ChrisSweens1 @Uromigos
https://t.co/Sr5myx9C6j
Improved MFS w/ darolutamide in DASL-HiCaP!
📌 1,106 very high-risk prostate cancer pts, incl persistent/rising PSA after RP. Randomised to darolutamide vs placebo w/ ADT + RT.
📌 Median age 71; GS 9-10 73%; CT N+ 29%; prior RP 15%.
📌 4y MFS on conventional imaging: 95% vs 88%, HR 0.42 (95% CI 0.27-0.66). No clear OS benefit yet.
📌 All prescribed prostate/bed AND pelvic nodal RT, w/ 96 wk ADT.
📌 N+ = CT/MRI >10 mm short axis or path confirmation (PSMA PET alone insufficient if ≤10 mm).
Side note: RT dose/fx and PSMA staging use aren't reported in the abstract. #radonc #ESMO26 #PCSM
View post on X ↗ PROTEUS substudy: perioperative apalutamide + ADT vs prostatectomy alone
Open-label substudy, randomized 1:3, N=408: apalutamide + ADT around radical prostatectomy and pelvic lymph node dissection (n=102) vs surgery alone (n=306), in high-risk localized or locally advanced disease. EFS HR 0.38 (95% CI 0.26–0.55), P<0.0001; 36-month EFS 63.0% vs 41.4%; median EFS 19.1 months with surgery alone. Metastasis-free survival, a secondary endpoint: HR 0.49 (0.26–0.90), nominal P=0.0193. Time to first subsequent therapy HR 0.29 (0.20–0.43), nominal. (ESMO 2026 LBA53 slides, Alberto Briganti; clinical cutoff Jul 13, 2026) The substudy is separate from the double-blind PROTEUS main trial presented at ASCO 2026. Perioperative apalutamide is investigational; apalutamide is FDA approved in nmCRPC and mCSPC. (KOL Pulse PROTEUS page)
PROTEUS substudy event-free survival. Alberto Briganti, ESMO 2026, LBA53. Photo posted by
@alantanmd.
Physicians saw the substudy as addressing a criticism of the main trial, which had no surgery-alone control. One physician reported that the discussant, Nicholas van As, concluded longer follow-up is needed before changing practice.
Answers an objection; follow-up still short
Esciting presentation by @Albert0Briganti ! PROTEUS substudy: adding perioperative apalutamide + ADT to surgery improved EFS in high-risk localized/locally advanced PCa (HR 0.38). Important randomized evidence for intensification! @myESMO #ESMO26 @oncoalert
https://t.co/QpfB0YpW6j
Among the big news from #ESMO2026: PROTEUS companion RCT (not a substudy ¯\_(ツ)_/¯ ) comparing neoadj apa/ADT to RP alone. Impressive early results, should put to rest at least some of the objections to PROTEUS main paper.
https://t.co/DTnUeyXi2D
At #ESMO26, Alberto Briganti presented the PROTEUS substudy, reporting improved EFS with perioperative apalutamide + ADT (HR 0.38).
Nicholas van As discussed key limitations and concluded that longer follow-up is needed before changing clinical practice.
#ProstateCancer
https://t.co/WpztxJBIPh JNJ-6143: a first-in-class oral AR-targeted RIPTAC in mCRPC
Phase 1 dose-escalation study presented by Benjamin Garmezy (2216O) in heavily pretreated metastatic castration-resistant prostate cancer. JNJ-6143 is investigational. Source: 2216O abstract, ESMO 2026 program.
JNJ-6143 PSA responses by dose and molecular features. Benjamin Garmezy, ESMO 2026, 2216O. Photo posted by
@katy_beckermann.
Physicians highlighted the new mechanism and activity across molecular subgroups, with the caveat that these are Phase 1 data.
New mechanism; early data
JNJ-6143, first-in-class oral AR-BRD4 RIPTAC, phase 1 mCRPC: a wide window between efficacy and safety. n=105, doses 12.5 to 150 mg.
📈 50 mg daily: PSA50 77%, PSA90 48%, confirmed ORR 69%, after a median 4 prior lines
📊 PSA declines seen from 12.5 to 150 mg. 66% of all patients still on drug
🔍 At 50 mg: 58% any-grade TRAEs, no serious TRAEs. Median DOR 11.0 months, CI 5.9 to NE
Activity across a 12-fold dose range. Phase 2 is open at 50 mg.
Congrats to @BGarmezy on the presentation and all the investigators.
#ESMO26 #ProstateCancer #mCRPC #GUonc
View post on X ↗
@BGarmezy with 1st report of an AR RIPTAC - JNJ-6143 in metastatic castration resistant #prostatecancer showing good PSA responses across aggressive molecular subtypes, median duration 11 months. New mechanism to degrade androgen receptor is active!
@oncoalert #ESMO26 @myESMO
https://t.co/ejTYkqTkgw
Promising #ESMO2026 data for JNJ-6143, a first-in-class oral RIPTAC in heavily pretreated #mCRPC.
PSA50 77% | PSA90 48% | ORR 69%
Encouraging activity, including in high-risk molecular subgroups. Early phase I, but one to watch.
#ProstateCancer
https://t.co/59WZYQMAQ9 Also discussed
PEACE-1 long-term OS (posts), TROPHY-U-01 (posts), CAPItello-281 (posts) and PE-PE, pembrolizumab after metastasis-directed therapy in oligometastatic RCC, presented on October 25 by Roberto Iacovelli (posts).
KEYNOTE-564: Toni Choueiri presented the final protocol-prespecified analysis of adjuvant pembrolizumab vs placebo in clear cell RCC on October 25 (3589RO). Physicians pointed to the durability of the benefit. KEYNOTE-564 trial page.
KEYNOTE-564 final analysis
@DrChoueiri w last, very last update of #Keynote564 pembrolizumab for adjuvant #kidneycancer. Ongoing overall survival benefit — even 7+ years out.
@oncoalert #ESMO26 @myESMO
https://t.co/RzNWvKHPuq KOL Voices: the top GU physicians at ESMO 2026
The ten GU physicians at the top of the ESMO 2026 Top KOLs leaderboard. One line from each, verbatim and linked, with the trial it is about.
What’s yet to come
GU sessions still ahead. Times are Madrid time.
October 26–27
- Mon Oct 26, 08:30-10:00 (Madrid) · Educational: How to optimise care for patients receiving prostate cancer systemic therapy, Bilbao Auditorium - Hall 3. Optimising therapy for locally advanced prostate cancer 08:30; Personalised systemic therapy for mHSPC 08:55; Management of mCRPC 09:20. Speakers: Barbara Jereczek-Fossa; Aurelius G. Omlin; Deborah Mukherji.
- Mon Oct 26, 10:15-11:00 (Madrid) · Challenge your expert: Challenges in the management of neuro-endocrine and small cell prostate cancer, Granada Auditorium - Hall 4. Presentation by expert 10:15; discussion 10:35. Speakers: Himisha Beltran; chair Ravindran Kanesvaran.
- Mon Oct 26, 10:15-11:30 (Madrid) · Multidisciplinary: Response-based adaptive strategies in primary metastatic kidney cancer, Leon Auditorium - Hall 4. Image-guided strategy 10:20; What to do with the primary in extreme responders 10:40; Timing and optimal local treatment for metastatic disease 11:00. Speakers: Viktor Grünwald; Geraldine Pignot; Shankar Siva.
- Mon Oct 26, 14:45-16:00 (Madrid) · Multidisciplinary: Optimal multidisciplinary management of penile cancer, Cordoba Auditorium - Hall 4. Surgery 14:50; adjuvant chemotherapy 15:10; radiation therapy 15:20; distant recurrence 15:40. Speakers: Maarten Albersen; Fernando C. Maluf; Angela U. Pathmanathan.
- Tue Oct 27, 09:00-13:00 (Madrid) · Scientific Congress Highlights 1, Almeria Auditorium - Hall 9. GU prostate, penile and testis 09:20-09:40; GU renal and urothelial 09:40-10:00. Speakers: Christopher J Sweeney; Bernadett E. Szabados.
Regulatory: durvalumab + EV from VOLGA is under FDA Priority Review. (KOL Pulse VOLGA page) Physician posts on new GU readouts are added to the ESMO 2026 trials page through October 27.
Related ESMO 2026 pages
FAQ
Which GU cancer trials did physicians discuss most at ESMO 2026?
By physician posts on X from October 23 to 25, the most-discussed GU trials were VOLGA, KEYNOTE-866, DASL-HiCaP, KEYNOTE-905, KEYNOTE-B15, ENERGIZE, LITESPARK-012, PROTEUS, LITESPARK-011, XmAb819 and JNJ-6143.
What did VOLGA show?
In cisplatin-ineligible or cisplatin-refusing MIBC, perioperative durvalumab plus 3 cycles of neoadjuvant enfortumab vedotin improved EFS (HR 0.51, 95% CI 0.38-0.67) and OS (HR 0.58, 0.40-0.83) vs control (ESMO 2026 LBA2, data cutoff Mar 2, 2026). It is investigational and under FDA Priority Review.
Why were KEYNOTE-866 and ENERGIZE negative?
Both added a PD-1 inhibitor to neoadjuvant gemcitabine-cisplatin and missed EFS (HR 0.88 and 0.94) despite higher pCR. Physicians on X pointed to control-arm outcomes, trial populations and biomarker selection. These are cross-trial observations, not head-to-head results.
What did the KEYNOTE-905 three-arm analysis add?
In an ad hoc, descriptive analysis of 255 concurrently randomized patients, EFS HR vs cystectomy alone was 0.40 with EV plus pembrolizumab and 0.71 with pembrolizumab alone (ESMO 2026 4733O, data cutoff Jun 6, 2025). Pembrolizumab alone is not approved for MIBC.
What did the LITESPARK-011 final analysis show?
Belzutifan plus lenvatinib did not significantly improve overall survival vs cabozantinib after PD-1/PD-L1 therapy: HR 0.85 (95% CI 0.70-1.03), one-sided P=0.04689 vs a boundary of 0.0223 (ESMO 2026 3587O, final analysis, data cutoff Feb 2, 2026). PFS (HR 0.74) and response benefits were maintained. The combination has been FDA approved since September 24, 2026, based on PFS and ORR.
What are XmAb819 and LITESPARK-012?
XmAb819 is an investigational ENPP3 x CD3 T-cell engager; Sumanta K. Pal presented Phase 1 data in heavily pretreated clear cell RCC. LITESPARK-012 is a Phase 3 trial in which adding belzutifan or quavonlimab to first-line pembrolizumab plus lenvatinib did not improve PFS or OS. Both triplets are investigational.
Is perioperative apalutamide approved for localized prostate cancer?
No. The PROTEUS substudy showed EFS HR 0.38 (95% CI 0.26-0.55) vs prostatectomy alone (ESMO 2026 LBA53), but perioperative use is investigational. Apalutamide is FDA approved in nmCRPC and mCSPC.