Conference · for clinicians

Asco gi 2026

1/11/2026 · 5 min read · updated 28 Oct 2026

Bottom line

Zanidatamab ± tislelizumab + chemo beat trastuzumab + chemo in HER2+ gastro-oesophageal adenocarcinoma. Encorafenib + cetuximab works with FOLFIRI as well as FOLFOX in BRAF V600E mCRC. In dMMR mCRC, adding FOLFOX-bev to atezolizumab improved PFS but with more toxicity.

HERIZON-GEA-01 — HER2+ gastro-oesophageal adenocarcinoma (first line)

Phase 3, n=914 (A 308 / B 304 / C 302). Arms: trastuzumab + chemo (A), zanidatamab + chemo (B), zanidatamab + tislelizumab + chemo (C); chemo = CAPOX or FP. Mandatory antidiarrhoeal prophylaxis. Median follow-up 25.9 mo. [NEJM 2026]
PFS: 8.1 (A) vs 12.4 (B; HR 0.65, 95% CI 0.52–0.81) vs 12.4 mo (C; HR 0.63, 0.51–0.78); P<0.001 for both.
OS (interim): 19.2 vs 24.4 (B; HR 0.80, 0.64–1.01, p=0.06, not significant) vs 26.4 mo (C; HR 0.72, 0.57–0.90, p=0.004).
Grade ≥3 AEs (published paper): 74.5% (A) / 73.8% (B) / 83.3% (C). Grade ≥3 diarrhoea 12.9% / 20.0% / 24.8%. [NEJM 2026] (Earlier symposium figures of 60% / 59% / 72% are superseded by the full paper.)
FDA, 25 Aug 2026: zanidatamab + tislelizumab + chemo approved for HER2 IHC 3+ or IHC 2+/ISH+ disease; zanidatamab + chemo (no PD-1) only for IHC 3+, because the arm B effect was mainly in IHC 3+ tumours (exploratory: PFS 14.2 vs 7.6 mo, HR 0.55). The zanidatamab label carries a boxed warning for diarrhoea and embryo-fetal toxicity. [FDA 2026]

HERIZON-GEA-01: median survival (months)

PFS: trastuzumab + chemo8.1 mo

PFS: zanidatamab + chemo12.4 mo

PFS: zani + tislelizumab + chemo12.4 mo

OS: trastuzumab + chemo19.2 mo

OS: zanidatamab + chemo24.4 mo

OS: zani + tislelizumab + chemo26.4 mo

Shitara et al., NEJM 2026 (same medians as the Jan 2026 symposium report). OS interim; arm B OS not significant.

BREAKWATER — BRAF V600E mCRC (first line)

Cohort 3 (n=147): encorafenib + cetuximab + FOLFIRI vs FOLFIRI ± bevacizumab. ORR (BICR, primary endpoint) 64.4% vs 39.2% (odds ratio 2.76, 95% CI 1.42–5.35; Abstract 13). [JCO 2026 Abstract 13] Later analysis (cut-off 6 Jan 2026): PFS 15.2 vs 8.3 mo, HR 0.44 (95% CI 0.27–0.70); OS HR 0.56 (0.34–0.94; median not estimable vs 20.3 mo). Serious AEs 49.3% vs 44.1%. [Ann Oncol 2026] This extends the FOLFOX-based BREAKWATER result (PFS 12.8 vs 7.1 mo, HR 0.53; OS 30.3 vs 15.1 mo, HR 0.49). The 2024 accelerated approval became a traditional FDA approval on 24 Feb 2026, now covering encorafenib + cetuximab with any fluorouracil-based chemotherapy, FOLFIRI included. [FDA 2026]

COMMIT — dMMR/MSI-H mCRC

n=102 (randomised phase 3 NRG-GI004/SWOG-S1610; chemo-bev arm closed after 20 patients because of KEYNOTE-177, leaving 41 vs 41). mFOLFOX6 + bevacizumab + atezolizumab vs atezolizumab alone: PFS HR 0.439 (95% CI 0.23–0.84; P=0.0103, primary analysis); updated (median follow-up 46 mo) median PFS 24.5 vs 5.3 mo (HR 0.42); 24-month PFS 53.7% vs 31.6%. ORR 86.1% vs 46%; primary progression 2.8% vs 32.4%. More grade ≥3 AEs (34 vs 18 patients) and grade 5 events (4 vs 1). [JCO 2026]

COMMIT: dMMR mCRC

Median PFS: FOLFOX-bev + atezo24.5 mo

Median PFS: atezo alone5.3 mo

COMMIT, J Clin Oncol 2026 (updated cut-off 6 Nov 2025): 24.5 mo (95% CI 10.1–NE) vs 5.3 mo (2.2–18.2).

COMMIT's single-agent arm PFS looks low compared with KEYNOTE-177/CheckMate-8HW; I would not abandon IO-only (or nivolumab–ipilimumab) for dMMR mCRC on this trial alone.

Practical take-aways for the clinic

HER2-positive gastric/GEJ: confirm HER2 by IHC (and ISH for 2+); zanidatamab-based regimens require proactive diarrhoea management. Pembrolizumab + trastuzumab + chemotherapy (KEYNOTE-811) remains an alternative standard for PD-L1 CPS ≥1 disease in many guidelines; HERIZON-GEA-01 is now published (NEJM 2026) and FDA-approved (Aug 2026). The PD-1-free zanidatamab regimen is labelled only for IHC 3+, and final OS for arm B is still awaited.
BRAF V600E colorectal: test BRAF together with RAS and MMR at diagnosis. Both FOLFOX- and FOLFIRI-based encorafenib + cetuximab schedules now have randomised data, allowing a choice based on neuropathy risk and prior oxaliplatin.
dMMR colorectal: immunotherapy first. KEYNOTE-177 established pembrolizumab over chemotherapy (PFS 16.5 vs 8.2 months, HR 0.60, 95% CI 0.45–0.80), [NEJM 2020] and nivolumab + ipilimumab is a further option. COMMIT asks whether adding chemotherapy helps — interesting, but toxicity was higher.

Other themes from the symposium

Biomarker-first GI oncology: HER2, MMR/MSI, BRAF, Claudin 18.2 and PD-L1 CPS now each change first-line therapy somewhere in the GI tract. Ordering them together on the diagnostic biopsy saves weeks.
Toxicity management as part of the regimen: HERIZON-GEA-01 mandated antidiarrhoeal prophylaxis — a reminder that supportive care protocols are part of reproducing trial results.
Chemotherapy backbones still matter: both BREAKWATER cohorts and COMMIT combined new agents with FOLFOX/FOLFIRI, the regimens most Indian centres already deliver well.

Reading conference data

Symposium data are often presented before peer review; numbers can change at publication. Interim OS analyses (as in HERIZON-GEA-01) may not be final, and subgroup analyses are exploratory. Where full papers exist, the figures above are taken from them; as of 28 Oct 2026, all three headline trials (HERIZON-GEA-01, BREAKWATER Cohort 3, COMMIT) have full publications.

The original oncosphere.in article was image-based and could not be recovered; this is a rewritten, referenced version under the same title.

Sources

Educational summary, not medical advice. Opinions are labelled as such and are the author's own. Approvals and availability in India (CDSCO) may differ from the US/EU.

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