Physician discussion, October 23–26

Physician posts on X, October 23–26.

The two endometrial cancer trials in Presidential Symposium III on October 26, TroFuse-005 and KEYNOTE-C93, went straight to the top of the gynecologic cancer table on the day they were presented. Before them, NRG-GY020, DUO-E and BEHOLD-1 drew the most physician posts; Kathleen Moore wrote many of them, in threads on each readout. 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).

Day 4: two endometrial cancer trials in Presidential Symposium III

TroFuse-005: sacituzumab tirumotecan after platinum and immunotherapy

TroFuse-005 (ENGOT-en23/GOG-3095; Merck) is a Phase 3 trial of sacituzumab tirumotecan (sac-TMT), a TROP2-directed antibody-drug conjugate, vs doxorubicin or paclitaxel (treatment of physician’s choice) in 776 patients with advanced or recurrent endometrial cancer after platinum chemotherapy and immunotherapy. Domenica Lorusso presented it on October 26 (LBA11); Joyce Liu was the invited discussant, and the results were published in The Lancet. Both dual primary endpoints were met at the prespecified interim analysis. Median OS was 19.0 vs 12.1 months, HR 0.68 (95% CI 0.55–0.84), one-sided P=0.0001. Median PFS by blinded independent central review was 7.2 vs 3.9 months, HR 0.59 (0.50–0.70), one-sided P<0.0001. Confirmed ORR by blinded independent central review, a key secondary endpoint, was 35.1% vs 17.3%. (ESMO 2026 LBA11 abstract and slides, Domenica Lorusso; interim analysis, data cutoff Mar 23, 2026) Grade ≥3 treatment-related AEs occurred in 54.4% vs 41.4%, and 3.1% vs 4.9% discontinued for treatment-related AEs. Among adverse events of special interest (any grade, regardless of attribution), oral mucositis/stomatitis occurred in 57.0% vs 17.4%, ocular surface toxicity in 30.5% vs 6.8% and anemia in 71.4% vs 46.6%. (LBA11 abstract and slides; data cutoff Mar 23, 2026) Sac-TMT is investigational in endometrial cancer and is not approved by the FDA or EMA for any use. Merck reports that the FDA accepted a Biologics License Application for priority review in this setting, with a target action date of June 15, 2027. (Merck press release, Oct 26, 2026) Sac-TMT is a different drug from sacituzumab govitecan.

Physicians posting on X described the survival benefit as clinically meaningful in a setting with few options. The concern was toxicity: Kathleen Moore listed stomatitis, ocular toxicity and anemia, said the drug requires aggressive counseling and mitigation, and hoped other ADCs in Phase 3 will match the efficacy with better tolerability.

Clinically meaningful, and the toxicity question

Kathleen Moore @DrKatyMoore

gynecologic oncologist; deputy director, Buffett Cancer Center · Oct 26

TroFuse-005/GOG-3095 (Lorusso, #ESMO26): Options after carbo/paclitaxel/ICI in recurrent endometrial cancer are limited and poor. Sac-TMT is the first TOP1 ADC to read out positive in phase 3: PFS HR 0.59 (7.2 vs 3.9 mo), ORR 35% vs 17%, plus an OS benefit. That is clinically meaningful and warrants use. The tox is a concern. Stomatitis 57% (mostly low grade, needs prophylactic steroid mouthwash), ocular 31%, anemia 71%. Requires aggressive counseling and mitigation. Several other ADCs are in phase 3, and I hope they match this efficacy with better tolerability. Time will tell. @myESMO

View post on X ↗

Christi Kim @ChristiKimMD

medical oncologist, breast and gynecologic cancers · Oct 26

Trop2 ADC Sac-TMT in Recurrent Advanced Endometrial Cancer significantly improved OS, PFS, DOR, double the ORR (TroFuse-005) #EndometrialCancer https://t.co/cYXDyaLoQA

View post on X ↗

Ana Maderuelo @anamg_98

medical oncology resident, Hospital Universitario 12 de Octubre, Madrid · Oct 26

🩷 #ESMO26 TroFuse-005 (ph III): sacituzumab tirumotecan vs chemo after platinum + IO in advanced endometrial cancer. PFS 7.2 vs 3.9 mo (HR 0.59) OS 19.0 vs 12.1 mo (HR 0.68) ORR 35% vs 17% Potential new option; monitor stomatitis and cytopenias. #gynonc https://t.co/q21z0FcOGy

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KEYNOTE-C93: first-line pembrolizumab alone vs chemotherapy in dMMR disease

KEYNOTE-C93 (GOG-3064/ENGOT-en15; Merck) is an open-label Phase 3 trial of first-line pembrolizumab alone vs carboplatin-paclitaxel in 299 patients with mismatch repair-deficient (dMMR) advanced or recurrent endometrial carcinoma. Brian M. Slomovitz presented it on October 26 (LBA12); Christian Marth was the invited discussant, and the results were published in The Lancet. The trial has two primary endpoints. At the prespecified interim analysis, PFS by blinded independent central review met its endpoint: median 38.2 vs 8.4 months, HR 0.57 (95% CI 0.42–0.79), one-sided P=0.0002. Overall survival did not meet its significance criterion at this interim analysis: HR 0.77 (0.52–1.15), with median OS not reached in either arm. In the chemotherapy arm, 85.2% of patients with progression received crossover pembrolizumab or another PD-1/PD-L1 inhibitor. (ESMO 2026 LBA12 abstract and slides, Brian M. Slomovitz; The Lancet; interim analysis, data cutoff Apr 24, 2026) Grade ≥3 treatment-related AEs occurred in 18.1% vs 50.7%. (LBA12 abstract; data cutoff Apr 24, 2026) First-line pembrolizumab monotherapy is investigational and not an FDA- or EMA-approved use. Approved first-line regimens in the US combine immunotherapy with carboplatin-paclitaxel, followed by maintenance immunotherapy; KEYNOTE-C93 did not compare pembrolizumab alone with any of them. (KEYTRUDA, JEMPERLI and IMFINZI US prescribing information; The Lancet)

Physicians welcomed a potential chemotherapy-free first-line approach with far less toxicity. The debate was the control arm: the trial compared pembrolizumab with chemotherapy alone, not with chemotherapy plus immunotherapy. The discussant, Christian Marth, put the question on screen, and Amol Akhade and Ana Maderuelo raised the same caveat. Overall survival is still immature.

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.

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.

One post on two ovarian ADC readouts

Mali Barbi, MD MSc | Breast & Gyn Oncologist @DrBarbiOnc

breast and gynecologic oncologist, Northwell Health · Oct 24

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

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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.

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.

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.

Physicians noted the single-arm design and asked how patients should be selected: by cyclin E1 overexpression on IHC or by CCNE1 amplification.

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.

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.

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.

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.

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.

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

Aya Mohamed | MSc, MD 🎗 @Dr_Oncologista

medical oncologist · Oct 24

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

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Oncology Brothers @OncBrothers

community oncologists Rohit and Rahul Gosain · Oct 24

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

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Dr Amol Akhade @SuyogCancer

medical oncologist · Oct 24

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

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MV Chandrakanth @ChandrakanthMv

medical oncologist, Narayana Health Kolkata · Oct 25

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.

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.

1. 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.”
2. JOSE ALEJANDRO PEREZ FIDAL (@PerezFidal), medical oncologist: on BEHOLD-1 → “Happy to see that translational studies are also oral communications in #ESMO2026.”
3. Sushil (@Sushilberiwal), radiation oncologist, posting before the congress on October 5: on INTERLACE “The INTERLACE is not positioned as routine intensification .”
4. 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 27

The last gynecologic cancer session of ESMO 2026. Time is Madrid time.

Physician reactions keep appearing 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 23-26, TroFuse-005 (16 posts from 12 physicians) and KEYNOTE-C93 (13 from 9), both presented on October 26, led the gynecologic cancer readouts, followed by NRG-GY020, DUO-E and BEHOLD-1 (mocertatug rezetecan).

What did TroFuse-005 show at ESMO 2026?

In endometrial cancer after platinum chemotherapy and immunotherapy, sacituzumab tirumotecan (sac-TMT) improved overall survival (19.0 vs 12.1 months, HR 0.68) and progression-free survival (7.2 vs 3.9 months, HR 0.59) vs doxorubicin or paclitaxel at the prespecified interim analysis (ESMO 2026 LBA11; data cutoff March 23, 2026). Grade 3 or higher treatment-related adverse events were more frequent (54.4% vs 41.4%). Sac-TMT is investigational in endometrial cancer; Merck reports that the FDA has accepted a Biologics License Application for priority review, with a target action date of June 15, 2027.

Is first-line pembrolizumab alone approved for dMMR endometrial cancer?

No. In KEYNOTE-C93 (ESMO 2026 LBA12), first-line pembrolizumab alone improved progression-free survival vs carboplatin-paclitaxel (38.2 vs 8.4 months, HR 0.57), but overall survival did not meet its significance criterion at the interim analysis. First-line pembrolizumab monotherapy is investigational, and the trial did not compare it with the approved chemotherapy-plus-immunotherapy regimens.

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.

Related ESMO 2026 pages

• TroFuse-005 trial page: full results, physician reactions and presented slides
• KEYNOTE-C93 trial page: full results, physician reactions and presented slides
• ESMO 2026 gynecologic cancer slides: presented slides by trial
• ESMO 2026 trials: physician posts by trial, including BEHOLD-1, NRG-GY020, DUO-E, INCB123667, torvutatug samrotecan, DENALI, KEYNOTE-B21, TroFuse-005 and KEYNOTE-C93
• ESMO 2026 conference page: themes, KOL leaderboard and live coverage