Physician discussion, October 23–25

Physician posts on X, October 23–25.

Also discussed: MASTERPLAN (posts), CheckMate 8HW (posts), AMPLIFY-7P (posts), and telisotuzumab adizutecan plus bevacizumab and CLARITY-Gastric01, both covered below.

1. SANO: active surveillance vs esophagectomy after clinical complete response

Phase 3 stepped-wedge, cluster-randomized trial, N=309, after neoadjuvant chemoradiotherapy (41.4 Gy). 5-year OS 50% with active surveillance vs 54% with surgery, HR 1.17 (95% CI 0.77–1.77), not significantly different; the confidence interval is wide and equivalence was not formally shown. DFS HR 1.39 (0.94–2.06). 5-year distant metastases 46% vs 29%, P<.01. 85 of 198 patients (43%) under surveillance were spared esophagectomy; the slide labels this figure hypothetical. (ESMO 2026 LBA78 abstract and slides, Sanjiv Gangaram-Panday; median follow-up 76 months) SANO tests a treatment strategy, not a drug.

SANO overall survival, active surveillance vs surgery. Sanjiv Gangaram-Panday, ESMO 2026, LBA78. Photo posted by @Dr_ElvinaA.

Physicians split on whether the trial supports offering surveillance. Points raised: the distant-metastasis rate, that a non-significant OS difference does not establish non-inferiority, and the 41.4 Gy dose.

2. HERIZON-GEA-01: zanidatamab ± tislelizumab in first-line HER2+ gastroesophageal adenocarcinoma

Phase 3, N=914: zanidatamab + chemotherapy, with or without tislelizumab, vs trastuzumab + chemotherapy. At the second interim OS analysis, zanidatamab + chemotherapy improved OS vs trastuzumab + chemotherapy: median 22.9 vs 19.6 months, HR 0.76 (95% CI 0.62–0.93), P=0.0088; 36-month OS 31.5% vs 22.9%. The triplet vs trastuzumab + chemotherapy: median OS 27.0 vs 19.6 months, HR 0.65 (0.52–0.80), a descriptive analysis because significance was already met at the first interim; 36-month OS 39.8%. Triplet vs doublet: HR 0.81 (0.65–1.00), P=0.0502, not statistically significant. (ESMO 2026 LBA79 slides, Kohei Shitara; second interim analysis, data cutoff Jul 15, 2026; median follow-up 35.3 months) The safety profile was consistent with the first interim analysis. (LBA79 safety slide) FDA approved on August 25, 2026: Ziihera + Tevimbra + chemotherapy for HER2 IHC 3+ or IHC 2+/ISH+ disease, and Ziihera + chemotherapy for IHC 3+. (KOL Pulse HERIZON-GEA-01 page)

HERIZON-GEA-01 OS, zanidatamab + chemotherapy vs trastuzumab + chemotherapy. Kohei Shitara, ESMO 2026, LBA79. Photo posted by @Dr_Oncologista.

The doublet’s OS result was not debated. The debate was whether to add tislelizumab, given the P=0.0502 comparison and added toxicity.

3. COMPANION-002: tovecimig + paclitaxel in previously treated biliary tract cancer

Phase 2/3: tovecimig, a DLL4×VEGF-A bispecific antibody, plus paclitaxel vs paclitaxel alone after prior therapy for advanced biliary tract cancer, presented by Nilofer Azad. The trial met its primary endpoint of response rate and improved PFS. OS did not differ, and the presented slide describes the OS analysis as confounded by crossover from the paclitaxel arm. Tovecimig is investigational.

COMPANION-002 OS analysis and crossover. Nilofer Azad, ESMO 2026. Photo posted by @graokane.

An investigator on the trial highlighted response and PFS. Others pointed to the toxicity, the crossover, and first-line testing.

4. G-HOPE-001: arcotatug tavatecan in CLDN18.2-positive gastric/GEJ cancer, third line and later

Phase 3, China and Japan: arcotatug tavatecan (IBI343), a CLDN18.2-directed antibody-drug conjugate, vs treatment of physician’s choice after at least two prior lines, presented by Kohei Shitara. PFS and OS both improved; the OS result was reported at the second interim analysis. Physicians quoted figures from two analyses, the abstract’s first interim and the updated second interim in the presentation, so the numbers differ between posts. Arcotatug tavatecan is not FDA approved.

G-HOPE-001 OS at the second interim analysis. Kohei Shitara, ESMO 2026, LBA77. Photo posted by @ArndtVogel.

Physicians called it a new option after two lines. Open questions: OS maturity, patients previously treated with zolbetuximab, and the lack of a Western cohort.

5. ACTICCA-1: adjuvant gemcitabine-cisplatin vs capecitabine in resected biliary tract cancer

Phase 3, presented by Henning Wege. The primary DFS endpoint was not met. OS was numerically longer with gemcitabine-cisplatin but not statistically significant, and toxicity was higher.

ACTICCA-1 primary endpoint (DFS). Henning Wege, ESMO 2026, LBA21. Photo posted by @DrAngelaLamarca.

Physicians agreed it does not change the standard. They differed on whether gemcitabine-cisplatin is an option for selected patients.

6. RASolute 302: daraxonrasib by RAS genotype in previously treated pancreatic cancer

Phase 3, N=500. Primary results: median OS 13.2 vs 6.7 months with daraxonrasib vs chemotherapy, HR 0.40 (95% CI 0.30–0.53), overall population. (ASCO 2026 LBA5 / NEJM; data cutoff Feb 10, 2026) At ESMO 2026, Zev A. Wainberg presented subgroup analyses from the same data cutoff. OS HR by RAS genotype: G12D 0.49 (0.33–0.74), G12V 0.32 (0.19–0.54), G12R 0.61 (0.29–1.30), Q61 0.37 (0.09–1.44), no RAS mutation identified 0.43 (0.09–1.98). The G12R, Q61 and no-mutation groups were small (30 vs 31, 11 vs 11 and 9 vs 7 patients) and their confidence intervals cross 1. ORR by BICR in G12R was 7% vs 14%. (ESMO 2026 LBA82 slides; subgroup HRs from an unstratified Cox model; median follow-up 8.5 months) FDA approved on August 26, 2026 as Rasonque for metastatic pancreatic adenocarcinoma after at least one prior systemic therapy, or in patients who are not candidates for multiagent therapy. The label does not restrict use by RAS status. (KOL Pulse RASolute 302 page)

RASolute 302 OS by RAS genotype. Zev A. Wainberg, ESMO 2026, LBA82. Photo posted by @LorenzaRimassa.

Physicians agreed on the overall benefit. The question was RAS G12R.

7. KEYNOTE-975: pembrolizumab with definitive chemoradiotherapy in esophageal cancer

Phase 3: pembrolizumab or placebo with definitive chemoradiotherapy in unresectable esophageal or GEJ cancer, presented by Manish Shah. EFS was not improved in PD-L1 CPS ≥10 tumors, and OS was not formally tested. Pembrolizumab is not approved with definitive chemoradiotherapy for esophageal cancer.

KEYNOTE-975 EFS, PD-L1 CPS ≥10. Manish Shah, ESMO 2026. Photo posted by @DaisukeKotani.

Physicians agreed the trial was negative. Discussion turned to radiation dose, timing of immunotherapy relative to radiation, and toxicity.

8. HARMONi-GI1: ivonescimab + gemcitabine-cisplatin vs durvalumab + gemcitabine-cisplatin in first-line biliary tract cancer

Phase 3 (LBA8), presented by Jian Zhou on October 25 in Presidential Symposium II, with James J. Harding as invited discussant. The comparator, durvalumab plus gemcitabine-cisplatin, is the FDA-approved first-line standard from TOPAZ-1. Physicians reported a statistically significant OS improvement, with gains in PFS and response rate. Ivonescimab, a PD-1×VEGF bispecific antibody, is investigational in the US; its first FDA application, in EGFR-mutant lung cancer, is under review. (KOL Pulse HARMONi-A page)

HARMONi-GI1 subsequent anti-tumor therapy by arm. Jian Zhou, ESMO 2026, LBA8. Photo posted by @dr_yakupergun.

Physicians called the comparator appropriate and the OS result meaningful. Open questions: VEGF-related toxicity, a China-only population and short follow-up.

After the presentation, physicians called the survival gain meaningful, noted the added toxicity and asked whether the result applies outside China.

Yakup Ergün asked about subsequent therapy, meaning treatment given after the trial treatment, as reported on the presented subsequent anti-tumor therapy slide (Jian Zhou, LBA8).

9. PRABITAS: biweekly vs conventional trifluridine-tipiracil + bevacizumab in refractory colorectal cancer

Pragmatic, non-inferiority Phase 3 trial from Japan, presented by Hiroya Taniguchi and published in The Lancet. The biweekly (14-day) schedule was compared with the conventional 28-day schedule. OS met non-inferiority, with less grade ≥3 neutropenia on the biweekly schedule. Trifluridine-tipiracil plus bevacizumab is FDA approved for previously treated metastatic colorectal cancer; PRABITAS tested the dosing schedule, not a new drug.

PRABITAS overall survival. Hiroya Taniguchi, ESMO 2026, LBA31. Photo posted by @CathyEngMD.

Physicians agreed on the schedule. The debate was why it took a randomized trial, after earlier real-world and Phase 2 data.

10. IROCAS: adjuvant mFOLFIRINOX vs mFOLFOX6 in high-risk stage III colon cancer

Phase 3 (LBA29) in resected T4 and/or N2 colon cancer, presented today by Jaafar Bennouna with Jeffrey Meyerhardt as invited discussant, and published concurrently in Annals of Oncology. Adding irinotecan to adjuvant oxaliplatin-based chemotherapy did not improve 3-year DFS, the primary endpoint, and OS did not differ significantly. Diarrhea was more frequent with mFOLFIRINOX. All drugs in both regimens are approved; IROCAS tested whether intensifying the adjuvant regimen helps.

IROCAS primary endpoint, 3-year DFS. Jaafar Bennouna, ESMO 2026, LBA29. Photo posted by @dr_yakupergun.

Physicians agreed the trial answers the adjuvant irinotecan question. Discussion moved to what to try next in high-risk and ctDNA-positive stage III disease.

11. AZUR-1: dostarlimab alone in dMMR/MSI-H locally advanced rectal cancer

Global, single-arm Phase 2, N=154: dostarlimab for 9 cycles (6 months) in untreated stage II/III dMMR/MSI-H rectal cancer, presented today by Andrea Cercek (LBA87) with David Tougeron as invited discussant, and published concurrently in Annals of Oncology. The primary endpoint, cCR12 (clinical complete response sustained for 12 months) by independent central review, was 47% (54 of 116 evaluable patients). By investigator assessment, cCR12 was 68% (95% CI 60–76) of 144 evaluable patients. 110 of 154 patients (71%) were treated with dostarlimab alone, had no further treatment and had no disease progression at data cutoff; median follow-up was 26.3 months. (FDA approval notice, Oct 19, 2026, via KOL Pulse AZUR-1 page; data cutoff as reported by FDA) The central-review and investigator figures use different evaluable populations; the presented slide shows that investigators recorded complete responses earlier than central review. FDA granted accelerated approval on October 19, 2026: Jemperli (dostarlimab) for adults with stage II/III dMMR/MSI-H locally advanced rectal cancer, as determined by an FDA-authorized test. (KOL Pulse AZUR-1 page)

AZUR-1 cCR12 by investigator vs central review. Andrea Cercek, ESMO 2026, LBA87. Photo posted by @TapiaJC1.

Physicians called dostarlimab alone a new standard for these patients. The main caveat raised was the gap between investigator and central-review results.

Also new: CLARITY-Gastric01 and telisotuzumab adizutecan

CLARITY-Gastric01: sonesitatug vedotin in CLDN18.2-positive gastroesophageal cancer, second line and later

Phase 3 (LBA7): sonesitatug vedotin, a CLDN18.2-directed antibody-drug conjugate, vs investigator’s choice, presented by Rui-Hua Xu on October 25 in Presidential Symposium II, with Salah-Eddin Al-Batran as invited discussant. Physicians reported an OS improvement, while PFS did not meet its significance threshold. Sonesitatug vedotin is investigational.

CLARITY-Gastric01 overall survival in the third-line-or-later population, a dual primary endpoint. Rui-Hua Xu, ESMO 2026, LBA7. Photo posted by @dr_yakupergun.

After the presentation, physicians welcomed the OS result in later lines. Open questions were the missed PFS endpoint in the overall population, the role in second line and use after zolbetuximab.

Telisotuzumab adizutecan + bevacizumab in refractory metastatic colorectal cancer

Long-term follow-up of a randomized Phase 1 comparison (791RO): telisotuzumab adizutecan (Temab-A, ABBV-400), a c-Met-directed antibody-drug conjugate, plus bevacizumab vs trifluridine-tipiracil plus bevacizumab in third-line or later disease. Michael Cecchini presented it on October 24 in the lower GI rapid oral session; Lisa Salvatore discussed it. The paper was published concurrently in Annals of Oncology. Efficacy favored Temab-A plus bevacizumab, with hematologic toxicity the main concern. A Phase 3 trial is ongoing, and Temab-A is investigational.

Temab-A + bevacizumab vs trifluridine-tipiracil + bevacizumab, overall survival. Michael Cecchini, ESMO 2026, 791RO. Photo posted by @ArndtVogel.

KOL Voices: GI cancer leaderboard

The top physicians on the ESMO 2026 KOL leaderboard, GI tab. One line from each, verbatim, with the trial it is about.

1. 1
   Nicholas Hornstein GI medical oncologist, Northwell · 51.6K impressions, 22 posts

   on PRABITAS → “Do we really always need randomized data to change practice?”
2. 2
   MV Chandrakanth medical oncologist, Narayana Health Kolkata · 48.7K impressions, 63 posts

   on SANO → “Surgery when needed — NOT surgery never!”
3. 3
   Nieves Martinez Lago MD PhD GI medical oncologist · 44.1K impressions, 38 posts

   on PRABITAS → “💡 Same survival, less toxicity!”
4. 4
   Jeff Ryckman radiation oncologist · 34.2K impressions, 32 posts

   on KEYNOTE-975 → “Another reason not to assume IO helps every CRT backbone.”
5. 5
   Arndt Vogel liver cancer and precision oncology, Princess Margaret / MHH · 31.8K impressions, 28 posts

   on COMPANION-002 → “Active drug, but no OS benefit in 2nd line, could be explored in 1L”
6. 6
   Anirban Maitra GI pathologist and pancreatic cancer researcher · 31.2K impressions, 5 posts

   on Daraxonrasib + vopimetostat (Tango) study “Reduced toxicity data is particularly important as a lower Daraxonrasib dose can be used.”
7. 7
   Angela Lamarca HPB and NET medical oncologist · 22.0K impressions, 42 posts

   on COMPANION-002 → “👉Development continues”
8. 8
   Daisuke Kotani, MD, Ph.D 小谷 大輔 GI medical oncologist, National Cancer Center Hospital East · 21.7K impressions, 16 posts

   on SANO → “Despite no significant OS or DFS differences, the wide CIs and significantly higher distant mets rate highlight important challenges for implementing active surveillance in clinical practice.”
9. 9
   Shankar Siva radiation oncologist, Peter MacCallum Cancer Centre · 20.2K impressions, 9 posts

   on MASTERPLAN → “Better efficacy without added harm.”
10. 10
    Erman Akkus medical oncologist · 17.4K impressions, 7 posts

    on HARMONi-GI1 → “mOS: 14.9 vs. 12.1 months; HR 0.75, 95% CI 0.61-0.92, P = 0.0031”

What’s yet to come: GI sessions on October 26–27

Times are Madrid time. Presidential Symposium III (October 26) has no GI abstracts.

FAQ

Which GI cancer trials did physicians discuss most at ESMO 2026?

By physician posts on X on October 23-25, the top GI trials were SANO, HERIZON-GEA-01, COMPANION-002, G-HOPE-001, ACTICCA-1, RASolute 302, KEYNOTE-975, HARMONi-GI1, PRABITAS, IROCAS and AZUR-1.

What did HERIZON-GEA-01 show at ESMO 2026?

At the second interim analysis (ESMO 2026 LBA79, data cutoff July 15, 2026), zanidatamab plus chemotherapy improved OS vs trastuzumab plus chemotherapy: 22.9 vs 19.6 months, HR 0.76 (95% CI 0.62-0.93), P=0.0088. Adding tislelizumab vs zanidatamab plus chemotherapy: HR 0.81, P=0.0502, not statistically significant. Both regimens have been FDA approved since August 25, 2026, with different HER2 criteria.

Does SANO show active surveillance is as good as surgery?

SANO found no statistically significant difference in 5-year OS (50% vs 54%, HR 1.17, 95% CI 0.77-1.77), but distant metastases were higher with surveillance (46% vs 29%). Equivalence was not formally shown, and physicians on X disagreed on whether to offer surveillance.

What was new for RASolute 302 at ESMO 2026?

Subgroup analyses (LBA82) showed OS hazard ratios below 1 across RAS genotypes, with small subgroups such as G12R (HR 0.61, 95% CI 0.29-1.30) having wide confidence intervals. Daraxonrasib (Rasonque) has been FDA approved since August 26, 2026 without a RAS-status restriction.

What did AZUR-1 show at ESMO 2026?

In 154 patients with untreated stage II/III dMMR/MSI-H rectal cancer given dostarlimab alone, cCR12 by independent central review (the primary endpoint) was 47% (54/116), and 68% by investigator assessment in 144 evaluable patients; 71% (110/154) had no further treatment and no disease progression at data cutoff (FDA notice, October 19, 2026). Dostarlimab (Jemperli) received FDA accelerated approval for this indication on October 19, 2026.

When were HARMONi-GI1 and CLARITY-Gastric01 presented?

Both were presented in Presidential Symposium II on October 25: CLARITY-Gastric01 (LBA7, Rui-Hua Xu; invited discussant Salah-Eddin Al-Batran) and HARMONi-GI1 (LBA8, Jian Zhou; invited discussant James J. Harding). Ivonescimab and sonesitatug vedotin are investigational in the US.

Which GI sessions are still ahead at ESMO 2026?

On October 26: a special symposium on upper GI cancer, a pancreatic cancer symposium, and the upper GI rapid oral session with LBA85, 3137RO, LEAP-012 long-term OS (1678RO), 1680RO, OPTIMUM (LBA22) and 473RO. On October 27: congress highlights for lower and upper GI cancers.

Related ESMO 2026 pages

• ESMO 2026 GI slide library
• ESMO 2026 trials: physician posts by trial
• ESMO 2026 conference page: daily highlights and KOL leaderboard
• HERIZON-GEA-01 trial page
• SANO trial page
• RASolute 302 trial page
• AZUR-1 trial page