The 2026 American Society of Clinical Oncology Gastrointestinal Cancers (ASCO GI) Symposium, held in January, brought together leading researchers and clinicians to share the latest advances in the treatment of gastroesophageal cancers. Many studies focused on using biomarkers (specific features of a tumour) to guide treatment decisions and improve outcomes, including targeted therapies and immunotherapy.

CRITICS-II Trial – Improving treatment before surgery in gastric cancer

The CRITICS-II study compared three different treatment approaches given before surgery in patients with gastric cancer that could be removed surgically: chemotherapy alone, chemotherapy followed by chemoradiotherapy, and chemoradiotherapy alone [1, 2]. This study demonstrated that patients who received chemotherapy followed by chemoradiotherapy had the best overall outcomes, including better short-term survival, a higher likelihood of the cancer disappearing at surgery, and fewer surgical complications. Chemotherapy alone led to the weakest results, while chemoradiotherapy alone was generally better tolerated but slightly less effective.

Key takeaway: Using a combination of treatments before surgery appears to improve outcomes compared with chemotherapy alone. However, longer follow-up and larger studies are needed before this approach becomes a new standard, especially given concerns about side effects.

HERIZON-GEA-01 Trial – A new generation of HER2-targeted treatment

Another major highlight was the HERIZON-GEA-01 trial, which evaluated a new targeted drug, Zanidatamab, in patients with advanced or metastatic gastroesophageal cancer who tested positive for HER2, a protein that can drive tumour growth. Zanidatamab, given together with chemotherapy (and in some cases also combined with the immunotherapy Tislelizumab), was compared with the current standard treatment of Trastuzumab plus chemotherapy [3, 4]. Patients treated with Zanidatamab lived longer without their cancer getting worse and showed deeper and longer-lasting responses than those receiving standard treatment.

Key takeaway: This study suggests that newer HER2-targeted therapies may replace current standard treatments and improve first-line care for patients with advanced or metastatic gastroesophageal cancer.

ILUSTRO Trial – Targeting CLDN18.2 in advanced or metastatic gastric and gastroesophageal cancer

The ILUSTRO study explored a treatment combination targeting Claudin 18.2 (CLDN18.2), a protein normally found in the stomach that becomes exposed on the surface of some gastric and gastroesophageal cancer cells. Patients whose tumours expressed this biomarker received a CLDN18.2-targeted antibody called Zolbetuximab, in combination with chemotherapy (mFOLFOX6) and immunotherapy (Nivolumab) [5]. Compared with previous treatments, this triplet combination helped patients live longer without disease progression, especially those with high levels of CLDN18.2. Side effects were manageable and in line with expectations for these treatments.

Key takeaway: CLDN18.2 is emerging as an important new target in gastric and gastroesophageal cancers, with treatments that combine a CLDN18.2-targeted antibody, chemotherapy, and immunotherapy showing the greatest benefit in patients whose tumours strongly express this biomarker.

Overall message: Together, the HERIZON-GEA-01 and ILUSTRO studies demonstrate how biomarker-based treatment is changing care for upper gastrointestinal cancers. By matching therapies to the biological features of each tumour, clinical care is moving toward more personalised, effective treatment for patients.

References:

[1]       Verheij M, van Grieken NCT, Slagter AE, et al. CRITICS-II: A multicenter randomized phase II trial of neo-adjuvant chemotherapy followed by surgery versus neo-adjuvant chemotherapy and subsequent chemoradiotherapy followed by surgery versus neo-adjuvant chemoradiotherapy followed by surgery in resectable gastric cancer. Journal of Clinical Oncology 2026; 44: 283.

[2]       Slagter AE, Jansen EPM, van Laarhoven HWM, et al. CRITICS-II: a multicentre randomised phase II trial of neo-adjuvant chemotherapy followed by surgery versus neo-adjuvant chemotherapy and subsequent chemoradiotherapy followed by surgery versus neo-adjuvant chemoradiotherapy followed by surgery in resectable gastric cancer. BMC Cancer 2018; 18: 877.

[3]       Tabernero J, Shen L, Elimova E, et al. HERIZON-GEA-01: Zanidatamab + chemo ± tislelizumab for 1L treatment of HER2-positive gastroesophageal adenocarcinoma. Future Oncology 2022; 18: 3255–3266.

[4]       Elimova E, Rha SY, Shitara K, et al. Zanidatamab + chemotherapy (CT) ± tislelizumab for first-line (1L) HER2-positive (HER2+) locally advanced, unresectable, or metastatic gastroesophageal adenocarcinoma (mGEA): Primary analysis from HERIZON-GEA-01. Journal of Clinical Oncology; 44. Epub ahead of print 10 January 2026. DOI: 10.1200/JCO.2026.44.2_suppl.LBA285.

[5]       Shitara K, Shoji H, Fazio N, et al. Phase 2 ILUSTRO trial of 1L zolbetuximab plus mFOLFOX6 and nivolumab in patients with CLDN18.2+ locally advanced (LA) unresectable or metastatic gastric or gastroesophageal junction (mG/GEJ) adenocarcinoma. Journal of Clinical Oncology 2026; 44: LBA284–LBA284.

Author:

Juliana Calheiros