New data presented at the 2026 ASCO Gastrointestinal Cancers Symposium (ASCO GI) highlight continued momentum across gastrointestinal oncology, with advances spanning molecularly defined colorectal cancer, HER2-positive upper GI malignancies, and systemic therapy strategies in hepatocellular and biliary tract cancers. Below, we summarise the most clinically relevant trials discussed, focusing on what was studied, the key findings presented,d and why each study matters for practice.
HERIZON-GEA-01
What is it?
HERIZON-GEA-01 is a phase III trial evaluating zanidatamab, a bispecific HER2-targeted antibody, combined with chemotherapy, with or without the PD-1 inhibitor tislelizumab, in patients with previously untreated HER2-positive metastatic gastroesophageal adenocarcinoma. The study was designed to assess whether zanidatamab-based regimens could improve outcomes beyond the longstanding trastuzumab-based standard.
Key findings as presented at ASCO GI
Zanidatamab-based combinations significantly improved progression-free survival compared with trastuzumab plus chemotherapy. Median PFS exceeded 12 months in the zanidatamab arms versus approximately 8 months with trastuzumab. Overall survival data were immature but favoured zanidatamab, particularly in the triplet arm that included tislelizumab. Response rates were higher and responses more durable, with a manageable safety profile consistent with prior studies.
Why it matters
These results suggest a potential new first-line standard of care for HER2-positive gastroesophageal cancer, a setting where survival gains have historically been incremental. The data also reinforce the growing role of bispecific antibodies and combination strategies in upper GI malignancies.
HER2 Uncovered: From Low to Ultralow – Get the Low Down with Ben Dessauvagie & Gelareh Farshid
BREAKWATER
What is it?
BREAKWATER is a phase III trial investigating the addition of encorafenib and cetuximab to FOLFIRI chemotherapy as first-line treatment for patients with BRAF V600E-mutated metastatic colorectal cancer (mCRC), a subgroup associated with aggressive disease and poor outcomes.
Key findings as presented at ASCO GI
The targeted triplet regimen produced a substantially higher objective response rate compared with standard chemotherapy-based approaches, with responses occurring earlier and lasting longer. Disease control was improved without introducing unexpected toxicities, and treatment discontinuation rates were comparable between arms.
Why it matters
BREAKWATER supports earlier integration of targeted therapy in BRAF-mutant mCRC and may reshape first-line treatment sequencing for this high-risk population, moving precision oncology further upstream in care pathways.
COMMIT
What is it?
The COMMIT trial evaluates first-line treatment strategies in dMMR/MSI-high metastatic colorectal cancer, comparing atezolizumab alone with atezolizumab combined with chemotherapy (mFOLFOX6) and bevacizumab. The study addresses whether immunotherapy alone is sufficient for all patients with immunogenic disease.
Key findings as presented at ASCO GI
Combination therapy significantly improved progression-free survival compared with atezolizumab monotherapy, with higher response rates and improved disease control. As anticipated, higher-grade toxicities were more frequent in the combination arm, reflecting the addition of chemotherapy and anti-angiogenic therapy.
Why it matters
COMMIT challenges the assumption that single-agent immunotherapy is always optimal in MSI-high mCRC. The results suggest that selected patients may benefit from combination approaches, particularly where early disease control is clinically important.
OrigAMI-1
What is it?
OrigAMI-1 is an early-phase trial assessing amivantamab, a bispecific antibody targeting EGFR and MET, in combination with standard chemotherapy (FOLFOX or FOLFIRI) in patients with RAS/BRAF wild-type metastatic colorectal cancer.
Key findings as presented at ASCO GI
The combination demonstrated encouraging and durable responses, with objective response rates exceeding 50% in some cohorts and a median progression-free survival of approximately 9 months. Activity was observed across subgroups, including patients with liver metastases, with a safety profile consistent with known toxicities.
Why it matters
Although early-phase, OrigAMI-1 highlights the potential of dual-pathway targeting beyond classic genomic drivers. These findings support ongoing phase III development and may expand biologic treatment options for a large proportion of mCRC patients.
Systemic Therapy Versus Locoregional Treatment in Intermediate-Stage HCC
What is it?
Data presented at ASCO GI explored systemic therapy approaches, including atezolizumab plus bevacizumab, compared with transarterial chemoembolisation (TACE) in patients with intermediate-stage hepatocellular carcinoma (HCC).
Key findings as presented at ASCO GI
Early analyses showed longer time to treatment failure and improved disease control with systemic therapy compared with TACE in selected patients. These findings suggest that immunotherapy-based regimens may outperform locoregional strategies in certain intermediate-stage settings.
Why it matters
This work adds to growing evidence that systemic therapy may challenge traditional locoregional standards in HCC, prompting reconsideration of treatment algorithms and multidisciplinary decision-making.
Targeted Therapy in FGFR2-Fusion Cholangiocarcinoma
What is it?
ASCO GI also featured updated data on FGFR inhibitors, including lirafugratinib, in patients with FGFR2-fusion positive cholangiocarcinoma who had progressed after prior therapy.
Key findings as presented at ASCO GI
Durable responses and meaningful disease control were observed in a difficult-to-treat population, with manageable toxicity. Activity was seen even in heavily pre-treated patients, reinforcing the role of molecular profiling.
Why it matters
For cholangiocarcinoma, where treatment options remain limited beyond first line, these findings reinforce precision oncology as a cornerstone of care and support broader genomic testing in routine practice.
GLP-1 Receptor Agonists and Colorectal Cancer Risk
What is it?
This was a large, real-world retrospective analysis examining the association between glucagon-like peptide-1 (GLP-1) receptor agonist use and the risk of developing colorectal cancer. Outcomes in people prescribed GLP-1 receptor agonists, commonly used for diabetes and obesity management, were compared with those taking low-dose aspirin, a drug frequently studied in cancer prevention research.
Key findings as presented at ASCO GI
Use of GLP-1 receptor agonists was associated with a significantly lower observed incidence of colorectal cancer compared with aspirin use. Overall, individuals receiving GLP-1 receptor agonists were approximately 36% less likely to develop colorectal cancer, with the reduction reaching around 42% in higher-risk subgroups. The association appeared consistent across age and body mass index categories, but was not observed in certain groups, including people with established atherosclerotic disease or active tobacco use.
Why it matters
Although observational and not evidence of causation, these findings raise important questions about the role of metabolic and inflammatory pathways in colorectal carcinogenesis. Given the increasing use of GLP-1 receptor agonists globally, the data may prompt further prospective research into cancer prevention strategies and encourage closer collaboration between oncology, endocrinology, and public health.
Physical Activity and Cancer-Related Fatigue in Colorectal Cancer Survivors
What is it?
This was a long-term, prospective cohort study assessing the relationship between post-diagnosis physical activity, particularly walking, and cancer-related fatigue among people treated for colorectal cancer. Participants were followed longitudinally with repeated symptom and quality-of-life assessments.
Key findings as presented at ASCO GI
Higher levels of moderate physical activity after diagnosis were associated with significantly lower reported fatigue scores over follow-up. Walking emerged as a particularly beneficial and accessible form of activity. The association was strongest in patients with non-metastatic disease, though improvements were observed across disease stages. Importantly, reductions in fatigue were sustained over time rather than limited to short-term follow-up.
Why it matters
Cancer-related fatigue remains one of the most common and burdensome survivorship symptoms. This study strengthens the evidence supporting physical activity as a core component of survivorship care, offering clinicians practical, low-risk guidance to support quality of life alongside ongoing oncologic management.
In summary
ASCO GI 2026 underscored continued progress across gastrointestinal oncology, with targeted and immunotherapy combinations, earlier use of precision strategies, and systemic therapies challenging established standards in liver and biliary cancers. Together, these trials point toward increasingly individualised treatment pathways, while also raising important questions about sequencing, toxicit,y and access that will shape future practice.
To explore further, visit the ASCO website or read the full press releases.
