Physician discussion, October 23–25
Physician posts on X, October 23–25.
Physician discussion of gynecologic cancer data on X has been concentrated: Kathleen Moore wrote about half of the posts above, in threads on each readout. Two of the highest-profile endometrial trials, TroFuse-005 and KEYNOTE-C93, have not been presented yet (see What’s yet to come). Two other October 24 readouts, both presented by Ana Oaknin, drew little physician discussion on X: REJOICE-Ovarian02, raludotatug deruxtecan plus bevacizumab (posts), and the BEATcc final overall survival analysis in cervical cancer (posts).
Ovarian cancer
BEHOLD-1: mocertatug rezetecan (B7-H4 ADC) in platinum-resistant ovarian cancer
Mocertatug rezetecan (Mo-Rez, GSK) is a B7-H4-directed antibody-drug conjugate with a topoisomerase I payload. Updated BEHOLD-1 results with longer follow-up (LBA41, Vanda Salutari) and a translational biomarker analysis (1248RO, Stephanie Lheureux) were presented on October 24; Camilla Nero was the discussant. Mo-Rez is investigational; the Phase 3 BEHOLD-Ovarian01 trial is enrolling.
BEHOLD-1 biomarker findings. ESMO 2026, 1248RO (Stephanie Lheureux). Photo posted by
@DrKatyMoore.
Physicians agreed that responses were seen across B7-H4 expression levels. The discussion was about what predicts response instead: linker cleavage and payload sensitivity rather than antigen level. Kathleen Moore also flagged the neutropenia that comes with the higher dose.
Responses across B7-H4 levels, and the cost of the higher dose
2/ Mocertatug rezetecan (MoRez) (B7-H4, TOP1i payload), BEHOLD-1, 136 patients with PROC.
Confirmed ORR 36% → 57% → 62% across 2.8, 4.8 and 5.8 mg/kg.
Median DoR 12.2 months at 5.8 mg/kg, with 90% still in response at 6 months.(Claudeai used to summarize)
https://t.co/tqx0Ob0dJQ
3/ The dose story is the toxicity story. From 4.8 to 5.8 mg/kg:
Grade ≥3 neutropenia 24% → 60%
Any-grade neutropenia 49% → 87%
ILD or pneumonitis 7% overall, 8/9 grade 1-2
Primary G-CSF is now recommended across the program.
https://t.co/6VZ829L7jz
4/ In the MoRez trial, 96% of the tumors were B7-H4 + and responses occurred at every expression level. Correlative work suggests Cathepsin B, TOP1 expression and matrix remodeling all associated with response.
https://t.co/cwJWw8ydje
Mo-Rez achieved activity even in patients with low expression of B7-H4. Nice translational data of the behold1 cathepsin B and Topo1 expression potential predictive biomarkers for Mo-Rez. Congrats to Dr Lhereux @LHeresy33502 for an outstanding presentation #ESMO2026 @myESMO
View post on X ↗ One post on two ovarian ADC readouts
Two #ovariancancer ADC readouts at ESMO 2026, and together they challenge how we select patients.
#BEHOLD_1 mocertatug rezetecan (B7-H4, TOPO1 payload), platinum-resistant ovarian: confirmed ORR 62% at 5.8 mg/kg, median DoR 12.2 mo. Responses at every B7-H4 level. Response tracked with cathepsin B, the enzyme that cleaves the linker, and with TOP1, the payload's target.
Torvutatug samrotecan (FRα, TOPO1 payload): ORR 48% in FRα ultralow/null, 57% low, 62% high, with overlapping CIs. ctDNA complete molecular response 47%, no clean link to FRα.
What I make of it:
With mirvetuximab, a DM4 payload, FRα-high was the gate. With TOPO1 payloads, the gate is falling. Nearly half of FRα-null tumors respond.
The biology that predicts response sits in the payload path: release and sensitivity, not antigen density.
That changes three things. Who we test: target IHC may exclude patients who would respond. How we sequence: after one TOPO1 ADC, the question is payload resistance, not a new target. How we design trials: stratify by payload biology, not by the antigen on the label.
Exploratory and single arm. But the direction is consistent, and it is where the field should look next. #gyncsm #ESMO26 @myESMO
View post on X ↗ FONTANA: torvutatug samrotecan (FRα ADC) in platinum-resistant ovarian cancer
Torvutatug samrotecan (Torvu-Sam, AZD5335, AstraZeneca) is a folate receptor alpha (FRα)-directed ADC with a topoisomerase I payload. Funda Meric-Bernstam presented updated FONTANA results on October 24 (1245RO); Philipp Harter was the discussant. The conclusions slide lists three Phase 3 ovarian cancer trials: TREVI-OC-01, TREVI-OC-02 and TREVI-OC-03. Torvu-Sam is investigational.
FONTANA conclusions. Funda Meric-Bernstam, ESMO 2026, 1245RO. Photo posted by
@PerezFidal.
Both physicians who posted noted activity across FRα expression levels. They read it differently: one asked whether a biomarker is needed at all; the other concluded that all patients with platinum-resistant disease can benefit.
Is FRα testing still needed?
5/ Torvutatug samrotecan (FRα/topo1)
ORR 48.1% in FRα ultralow/null, 57.1% low, 61.7% high. A gradient, yes. But the confidence intervals overlap , and nearly half of FRα-null tumors responded. So do we need a biomarker at all here?
https://t.co/m2mYihxMDD
Torvu-sam showed an encouraging activity with an ORR around 60% in both high and low FRalpha groups supporting that all PROC patients can benefit regardless of FRalpha expression. Results from Fontana trial. #Esmo2026
View post on X ↗ INCB123667 + bevacizumab: a CDK2 inhibitor in platinum-resistant ovarian cancer
INCB123667 (Incyte) is an oral selective CDK2 inhibitor, tested with bevacizumab in recurrent ovarian cancer. Domenica Lorusso presented the platinum-resistant cohort (1241RO, October 23); Iain McNeish discussed it with DENALI. INCB123667 is investigational.
INCB123667 plus bevacizumab, preliminary efficacy. Domenica Lorusso, ESMO 2026, 1241RO. Photo posted by
@DrBarbiOnc.
Physicians noted the single-arm design and asked how patients should be selected: by cyclin E1 overexpression on IHC or by CCNE1 amplification.
Activity, and who to select
2/8 INCB123667 + bev in PROC, n=23: 87% cyclin E1 overexpressed (35% of those CCNE1 amplified), 43% with ≥4 prior lines, 83% prior bev.
ORR 48% (confirmed 43%)
DCR 91%
mDOR 5.7 mo
mPFS 7.4 mo
https://t.co/dXGJFhswAK
INCB123667 + bev in #PROC. Selective CDK2 inhibitor, n=23. ORR 48%, mPFS 7.4 mo, responses after PARPi and after prior bev.
Single arm. Bev alone in PROC was about 16%. MAESTRA 3 will test CDK2i + bev vs bev.
87% cyclin E1 overexpressed, so IHC barely selects. We need response by CCNE1 amplification.
Endometrial was in phase 1. All three pivotal trials are ovarian. 28% of p53abn endometrial cancers carry CCNE1 amplification, enriched in carcinosarcoma. That cohort deserves its own trial. #gyncsm #ESMO26
View post on X ↗
3/8 Next: MAESTRA3 (NCT07797283), a phase 3 of INCB123667 + bev vs bev as first-line maintenance in cyclin E1-overexpressing EOC, starts in 2026. Cyclin E1 biology is heading to the front line.
View post on X ↗ DENALI (GOG-3066): azenosertib, a WEE1 inhibitor, in platinum-resistant ovarian cancer
DENALI Part 1b tested azenosertib, an oral WEE1 inhibitor, in platinum-resistant ovarian cancer and reported overall survival by cyclin E1 status (1242RO, Fiona Simpkins, October 23). Azenosertib is investigational. One physician posted about it: Kathleen Moore, in the same thread as INCB123667.
DENALI Part 1b, cyclin E1 positivity and outcomes. Fiona Simpkins, ESMO 2026, 1242RO. Photo posted by
@DrKatyMoore.
Kathleen Moore’s thread weighed the overall survival result against how cyclin E1 status was assigned, then turned to tolerability: dose interruptions, reductions and discontinuations.
A drug effect, or selection? And tolerability
4/8 DENALI Part 1b, azenosertib 400 mg 5 days on/2 off: n=102 PROC, median 3 prior lines, 91% prior bev, 55% PARPi, 15% MIRV. Cyclin E1 IHC+ in 51% of evaluable tumors vs CCNE1 amplification in 31%.
https://t.co/Fj6tVC5W50
6/8 OS benchmarks: ~13 mo with single-agent chemo (AURELIA), 16.9 mo with mirvetuximab in FRα-high disease (MIRASOL). High cyclin E1 usually carries worse prognosis, so a longer OS in cyclinE1+ tumors points toward a drug effect.
But: cyclin E1 status was assigned retrospectively with a proprietary cutoff, the CIs overlap and there is no control arm. ASPENOVA (azenosertib vs chemo, n≈420) and DENALI Part 2 will tell us if this holds.
View post on X ↗
7/8 Tolerability is the issue to solve: dose interruptions 57%, reductions 43%, discontinuations 20%, grade ≥3 fatigue 16% and thrombocytopenia 12%. Mitigation in Part 2a reportedly halved discontinuations to ~10%.
https://t.co/SBSZhPia0X
8/8 My takeaways: cyclin E1 overexpression by IHC is becoming the selection biomarker for CDK2 and WEE1 programs, reaching more patients than amplification.
View post on X ↗
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Endometrial cancer
NRG-GY020 and KEYNOTE-B21: pembrolizumab after surgery in dMMR endometrial cancer
NRG-GY020 (1239O, NRG Oncology/NCI) is a Phase 3 trial of adjuvant radiotherapy with or without pembrolizumab in stage I–II, high-intermediate-risk dMMR endometrioid endometrial cancer. It did not meet its primary endpoint. A ctDNA analysis of KEYNOTE-B21 (pembrolizumab with adjuvant chemotherapy in high-risk dMMR disease) was presented in the same session. Vicky Makker was the invited discussant for both and for DUO-E. Adjuvant pembrolizumab is investigational in these settings.
Discussant slide on NRG-GY020, KEYNOTE-B21 and DUO-E. Vicky Makker, ESMO 2026 proffered paper session, gynecologic cancers. Photo posted by
@SuyogCancer.
Physicians agreed the primary endpoint was negative. They disagreed on what that means: one kept radiotherapy alone as his default; another questioned whether the trial was designed to detect a realistic effect. On KEYNOTE-B21, the question was whether postoperative ctDNA can select patients, and whether a negative test is reliable enough to drive de-escalation.
Negative trial, or underpowered trial?
GY020 didn't meet its primary endpoint: 3y success 70% w/ pembro+RT vs 73% RT alone. Leaving study counted as failure.
KM RFS numerically favored pembro, but CI crossed 1. G3/4 toxicity 43% vs 15%. RT alone remains my default here.
#ESMO26 #radonc
https://t.co/tmjNMzulqN https://t.co/KR1rbuVzhW
@myESMO @FBackesMD
1/ NRG-GY020 at #ESMO26: RT ± 1 yr pembro in stage I/II high-intermediate risk dMMR endometrioid EC (n=168, 1:2). The primary endpoint, 3-yr recurrence-free status, was negative: 73% vs 77%, p=0.31. Question - is this really negative or is this a case of over aggressive statistical design to conserve sample size?
🧵
View post on X ↗
6/ GY020 doesn’t show that IO does nothing in early dMMR EC, and it doesn’t show that it helps. The question is still open. The next trial needs a realistic effect size and an endpoint that doesn’t count dropout as recurrence.
View post on X ↗ KEYNOTE-B21: can ctDNA select patients?
7/ Also at #ESMO26: the KEYNOTE-B21 ctDNA analysis in dMMR (Signatera, tumor-informed). Only ~20% were ctDNA+ after surgery (and importantly BEFORE chemo not after), and in stage I/II it was 5% and 18% (n=44). That’s lower than I expected for resected high-risk disease.
View post on X ↗
9/ The harder finding: in the placebo arm, 15 of 19 DSFS events occurred in pts who were ctDNA− at baseline (sensitivity 21%, NPV 80%). A negative postop test isn’t ready to drive de-escalation. (figure made with claude ai)
https://t.co/MbQBVeeIUR DUO-E: durvalumab with or without olaparib, updated overall survival
DUO-E (LBA37, Shannon Westin; AstraZeneca) is a Phase 3 trial of carboplatin-paclitaxel plus durvalumab, followed by durvalumab with or without olaparib maintenance, in advanced or recurrent endometrial cancer. The trial met its PFS endpoints earlier. At this interim analysis, the overall survival difference did not reach statistical significance. In the US, durvalumab with chemotherapy followed by durvalumab is FDA approved for dMMR disease. In the EU, the olaparib combination is approved for pMMR disease and durvalumab alone for dMMR disease.
DUO-E interim overall survival, ITT population. Shannon N. Westin, ESMO 2026, LBA37. Photo posted by
@Dr_Oncologista.
Physicians agreed the OS difference was not statistically significant at this analysis. They split on the olaparib question: one pointed to a numerical benefit in pMMR disease, another concluded the approach belongs only in dMMR disease, and a third asked whether added PFS justifies added toxicity.
dMMR, pMMR and the value of olaparib
DUO-E #ESMO26
Overall Survival Signals and the Added Value of PARP Inhibition in Advanced Endometrial Cancer
@OncoAlert #ESMOAmbassadors
#ESMOcommunity @myESMO
https://t.co/vfsuUFj0wf
6. DUO-E (Updated OS): PhIII, Durva + chemo → Durva + olaparib vs chemo alone in advanced/recurrent endometrial cancer.
- mOS 51.1 vs 39.6 mo (HR 0.77)
- Interim analysis did not meet formal statistical threshold
- Numerical benefit seen in pMMR
8/10
https://t.co/pgdlUuAvCy https://t.co/ququuaxl11
Conclusion in One line . Trial is negative for OS . And this approach should be used only in dMMR pts . #DUO-E @myESMO #esmo26 @OncBrothers @OncoAlert
https://t.co/EpRGmXsAtS
DUO-E | ESMO 2026 — PFS PASSED. OS STILL AWAITS VERDICT!
Three-part analysis of advanced/recurrent endometrial cancer.
Part 1: Rationale, trial design & PFS benefit.
Part 2: Median OS 51.1 vs 39.6 months (HR 0.77). An 11.5-month numerical gain, but formal interim significance not reached.
Part 3: Does olaparib truly add value? Incremental PFS benefit, greater toxicity, but unproven additional OS benefit over durvalumab alone.
The clinical question: Is the added PFS worth the toxicity while final OS remains awaited?
Ref: Westin SN et al. ESMO 2026; LBA37.
@myESMO @OncoAlert #MVOnco #ESMO26 #EndometrialCancer
View post on X ↗ On October 25, discussion continued with a comparison of the overall survival results from three first-line endometrial cancer trials: NRG-GY018, RUBY and DUO-E.
October 25: DUO-E beside NRG-GY018 and RUBY
THREE TRIALS. THREE OS STORIES!
NRG-GY018 vs RUBY vs DUO-E | Advanced/recurrent endometrial cancer.
🟢 NRG-GY018: Strong PFS benefit. dMMR OS HR 0.56 (nominal); pMMR HR 0.86 (NS).
🟣 RUBY: Overall OS formally positive (HR 0.69). Strong dMMR signal.
🔵 DUO-E: PFS positive. Interim OS not formally significant; incremental OS benefit from olaparib unproven.
OS SIGNAL ≠ OS PROVEN!
References: Eskander et al., NEJM 2023 (NRG-GY018); Mirza et al., NEJM 2023 & Powell et al., Ann Oncol 2024 (RUBY); Westin et al., JCO 2024 (DUO-E); updated OS: ASCO/ESMO 2026.
#ESMO26 #EndometrialCancer #MVOnco @myESMO @OncoAlert
View post on X ↗ KOL Voices: gynecologic cancers
The top physicians in the gynecologic cancer tab of the ESMO 2026 KOL leaderboard, with one line each in their own words and the trial it is about.
- Kathleen Moore (@DrKatyMoore), gynecologic oncologist: on NRG-GY020 → “If we want ctDNA to select who needs IO in early dMMR EC, we need more sensitive assays and testing that extends past 2-3 yrs.”
- JOSE ALEJANDRO PEREZ FIDAL (@PerezFidal), medical oncologist: on BEHOLD-1 → “Happy to see that translational studies are also oral communications in #ESMO2026.”
- Sushil (@Sushilberiwal), radiation oncologist, posting before the congress on October 5: on INTERLACE “The INTERLACE is not positioned as routine intensification .”
- Alfonso Cortés Salgado (@AlfonsoCorts9), medical oncologist: on the ESMO 2026 cervical cancer guidelines “Honoured to join Prof. Domenica Lorusso this morning at the @myESMO Clinical Session Guidelines, presenting the new ESMO cervical cancer guidelines”
What’s yet to come: October 25–27
Gynecologic cancer sessions still ahead. Times are Madrid time.
| When | Session | Trial or talk | Speaker |
|---|
| Sun Oct 25, 14:45–16:15 | Educational session: Cervical cancer: From prevention to optimal therapy (Bilbao Auditorium, Hall 3) | Challenges of prevention and screening (14:45); locally advanced disease: current and future options for improving survival (15:05); optimal systemic therapy for persistent, recurrent or metastatic disease (15:25); new developments in systemic therapy beyond CPIs (15:45) | Angelica N. Rodrigues; Domenica Lorusso; Ana Oaknin; Jung-Yun Lee; chairs Ana Oaknin, Christian Marth |
| Mon Oct 26, 08:30–10:00 | Special symposium: Navigating the wave of new therapies in gynaecologic cancers (Barcelona Auditorium, Hall 9) | DNA damage repair inhibition in ovarian cancer (08:30); new immunotherapy treatments and combinations (08:50); ADCs in gynaecological cancers (09:10); monitoring tumour response (09:30) | Charlie Gourley; Kathleen N. Moore; Toon Van Gorp; Pierre Laurent-Puig |
| Mon Oct 26, 10:15–11:30 | Multidisciplinary session: Optimal management of high-grade serous ovarian cancer with BRCA mutation (Cadiz Auditorium) | Surgery and first-line systemic therapy (10:20); oligoprogression (10:40); systemic therapy for recurrence during PARPi (11:00) | Sven Mahner; Remi Nout; Ilaria Colombo |
| Mon Oct 26, 17:18–17:42 | Presidential Symposium III (Alicante Auditorium, Hall 6) | LBA11 TroFuse-005: sacituzumab tirumotecan in previously treated advanced or recurrent endometrial cancer (posts) | Domenica Lorusso; discussant Joyce F. Liu |
| Mon Oct 26, 17:42–18:06 | Presidential Symposium III (Alicante Auditorium, Hall 6) | LBA12 KEYNOTE-C93: first-line pembrolizumab vs carboplatin-paclitaxel in dMMR advanced or recurrent endometrial carcinoma (posts) | Brian M. Slomovitz; discussant Christian Marth |
| Tue Oct 27, 10:20–10:40 | Scientific Congress Highlights 2 (Barcelona Auditorium, Hall 9) | Gynaecological cancers highlights | Antonio González-Martín |
Physician reactions to TroFuse-005 and KEYNOTE-C93 will appear on the ESMO 2026 trials page as they are posted.
FAQ
Which gynecologic cancer trials did physicians discuss most at ESMO 2026?
By physician posts on X on October 23-25, the most discussed were BEHOLD-1 (mocertatug rezetecan), DUO-E and NRG-GY020, followed by INCB123667 plus bevacizumab, FONTANA (torvutatug samrotecan), DENALI (azenosertib) and the KEYNOTE-B21 ctDNA analysis.
Are mocertatug rezetecan and torvutatug samrotecan approved?
No. Both antibody-drug conjugates are investigational. Phase 3 trials are under way or planned: BEHOLD-Ovarian01 for mocertatug rezetecan and the TREVI-OC trials for torvutatug samrotecan.
What did DUO-E show at ESMO 2026?
The updated overall survival analysis did not reach statistical significance at this interim analysis. Durvalumab with chemotherapy followed by durvalumab is FDA approved for dMMR advanced or recurrent endometrial cancer; the olaparib combination is approved in the EU for pMMR disease.
Did NRG-GY020 show a benefit for adjuvant pembrolizumab?
No. Adding pembrolizumab to adjuvant radiotherapy in stage I-II high-intermediate-risk dMMR endometrial cancer did not meet the primary endpoint. Physicians on X debated whether the trial was designed to detect a realistic effect.
When are TroFuse-005 and KEYNOTE-C93 presented?
Both are in Presidential Symposium III on Monday, October 26, in Madrid: TroFuse-005 (LBA11, Domenica Lorusso) at 17:18 and KEYNOTE-C93 (LBA12, Brian M. Slomovitz) at 17:42.
Related ESMO 2026 pages