Day 3 of the ESMO GI Cancers Congress 2026 brought several important updates in colorectal cancer and upper gastrointestinal cancers.
The discussions focused on ctDNA in resected colorectal liver metastases, adjuvant immunotherapy in dMMR colon cancer, KRAS G12C targeting in metastatic colorectal cancer, HER2-directed treatment in gastroesophageal adenocarcinoma, and TIGIT targeting in upper GI tumors.
ctDNA After Resection of Colorectal Liver Metastases
The benefit of postoperative adjuvant chemotherapy after curative-intent resection of colorectal liver metastases remains uncertain, with no consistent overall survival benefit. Clinical and tumor-related characteristics have been suggested to identify patients who may benefit from adjuvant chemotherapy in this setting.
A new GALAXY analysis explored whether ctDNA could help identify patients more likely to benefit from adjuvant chemotherapy after resection of colorectal liver metastases.
GALAXY: ctDNA and Adjuvant Chemotherapy After CRLM Resection
In abstract 8O, Kozo Kataoka presented an overall survival analysis in patients with metastatic colorectal cancer whose ctDNA status and dynamics were studied after resection of colorectal liver metastases. Patients’ ctDNA-based molecular residual disease status was assessed using the tumor-informed Signatera assay during the MRD window, defined as 2 to 10 weeks after surgery.
At a median follow-up of 43.2 months, MRD positivity was associated with shorter DFS and OS compared with MRD negativity. In the upfront surgery cohort, MRD-positive patients had worse DFS and OS, with HRs of 4.14 and 9.13, respectively.
Among MRD-positive patients in the upfront surgery cohort, adjuvant chemotherapy was associated with improved DFS and OS compared with observation. At 48 months, OS was 65.3% with adjuvant chemotherapy versus 32.9% with observation. This improvement was not seen in MRD-negative patients.
Patients who received neoadjuvant chemotherapy were analyzed separately. In this cohort, postoperative MRD positivity remained prognostic, but adjuvant chemotherapy was not associated with improved DFS or OS regardless of MRD status. These findings support postoperative ctDNA-based MRD as a potential stratifying tool after curative-intent resection of colorectal liver metastases, especially after upfront surgery. Prospective validation is still needed.
ATOMIC: The Question of Duration
ATOMIC previously showed that adding atezolizumab to adjuvant mFOLFOX6 improved DFS in patients with stage III deficient mismatch repair colon cancer. The remaining question was duration: does shorter chemotherapy exposure affect benefit, and is longer atezolizumab exposure needed?
In abstract 1O, Anke Reinacher-Schick presented a secondary analysis evaluating whether DFS was affected by the number of mFOLFOX6 or atezolizumab cycles received.
No DFS benefit from adding atezolizumab was seen among patients who received shorter chemotherapy exposure. Among patients who received 6 or fewer cycles of mFOLFOX6, 3-year DFS was similar with atezolizumab plus mFOLFOX6 and mFOLFOX6 alone: 80.0% versus 79.9%.
For atezolizumab duration, 3-year DFS was 84.0% among patients who received fewer than 12 cycles and 88.0% among those who received 12 or more cycles, with no significant difference.
This secondary exploratory analysis suggests that atezolizumab benefit was mainly seen with longer mFOLFOX6 exposure, while longer atezolizumab duration did not show a clear added benefit.
Read more about ATOMIC at ESMO GI 2026 on OncoDaily.
KRYSTAL-10: Adagrasib Plus Cetuximab vs Chemo in KRAS G12C mCRC
Data on RAS-targeting agents continue to evolve in metastatic colorectal cancer. In KRYSTAL-10, adagrasib, a KRAS G12C inhibitor, was combined with cetuximab as a chemotherapy-free regimen and compared with standard chemotherapy in the second-line setting.
In late-breaking abstract LBA1, Josep Tabernero reported the final analysis of KRYSTAL-10, a global, open-label, randomized phase 3 trial of second-line adagrasib plus cetuximab versus chemotherapy, with or without VEGF/VEGFR inhibitors, in patients with previously treated KRAS G12C-mutated metastatic colorectal cancer.
Patients were randomized to receive adagrasib 600 mg twice daily plus cetuximab 500 mg/m² every 2 weeks, or chemotherapy with FOLFIRI or mFOLFOX6, with or without VEGF/VEGFR inhibitors.
After enrollment of 461 patients and a minimum follow-up of 26.4 months for OS, the study did not meet its dual primary endpoints. Median PFS was 7.5 months with adagrasib plus cetuximab versus 8.1 months with chemotherapy (HR, 0.89; 95% CI, 0.71–1.13; p=0.32). Median OS was 21.6 months versus 21.7 months, respectively (HR, 0.83; 95% CI, 0.67–1.03; p=0.09).
ORR was higher with adagrasib plus cetuximab: 47% versus 16% with chemotherapy.
Prof. Per Pfeiffer commented on the “very long median OS in the control arm,” noting that this was difficult to interpret in patients with KRAS G12C-mutated metastatic colorectal cancer. Around 30% of patients in the control arm received KRAS G12C inhibitor therapy in subsequent lines, which may have affected OS but not PFS.
KRYSTAL-10 did not show superiority of adagrasib plus cetuximab over chemotherapy in the second-line setting, despite higher response rates. The results also raise questions about how KRAS G12C plus anti-EGFR strategies will fit in the era of multi-selective RAS inhibitors and newer combination approaches.
Read more about KRYSTAL-10 at ESMO GI 2026 on OncoDaily.
HERIZON-GEA-01: HER2 Targeting and Quality of Life
HER2-directed treatment was also discussed in upper GI cancers, with health-related quality-of-life data from HERIZON-GEA-01.
In abstract 494O, Kohei Shitara presented HRQoL results from HERIZON-GEA-01 in patients with first-line HER2-positive advanced or metastatic gastroesophageal adenocarcinoma.
HERIZON-GEA-01 evaluated zanidatamab plus chemotherapy, with or without tislelizumab, versus trastuzumab plus chemotherapy. Previous efficacy results showed improved PFS with both zanidatamab-containing regimens, and a significant OS benefit with zanidatamab plus tislelizumab plus chemotherapy.
The HRQoL analysis showed that physical functioning and global health status were generally maintained across treatment arms. Diarrhea was more frequent in the zanidatamab-containing arms and showed the greatest worsening among symptom scales.
These findings support zanidatamab-based treatment in HER2-positive advanced or metastatic gastroesophageal adenocarcinoma, with maintained overall health-related quality of life.
STAR-221: TIGIT Targeting in Upper GI Cancer
TIGIT is an inhibitory immune checkpoint co-expressed with PD-1 on T cells. Blocking TIGIT and PD-1 has been explored as a strategy to enhance the antitumor effect of immunotherapy.
In abstract 493O, Sun Young Rha presented the interim analysis of STAR-221, a phase 3 study comparing domvanalimab, an Fc-silent anti-TIGIT antibody, plus zimberelimab, an anti-PD-1 antibody, and chemotherapy versus nivolumab plus chemotherapy.
The study included patients with previously untreated HER2-negative advanced gastric, gastroesophageal junction, or esophageal adenocarcinoma.
STAR-221 did not show an OS improvement with the TIGIT-targeting regimen plus anti-PD-1 and chemotherapy. The HR for OS was 1.01 (95% CI, 0.86–1.17; p=0.526). No OS benefit was seen in patients with TAP ≥5% or TAP ≥1%. PFS and ORR were also similar between the two treatment arms.
The main takeaway from STAR-221, together with previous TIGIT studies in upper GI tumors, is that TIGIT targeting has not yet translated into a clear clinical benefit in this setting. Despite encouraging early-phase results, further refinement of patient selection and biomarker-driven strategies may be needed.
Takeaway
Day 3 highlighted both the value of biomarkers and the limits of several treatment intensification strategies in GI oncology. ctDNA-based MRD may help identify patients with resected colorectal liver metastases who are more likely to benefit from adjuvant chemotherapy, especially after upfront surgery. ATOMIC raised an important question about chemotherapy exposure in adjuvant immunotherapy for dMMR colon cancer, while longer atezolizumab duration did not show a clear added benefit.
KRYSTAL-10 did not show superiority of adagrasib plus cetuximab over standard chemotherapy in second-line KRAS G12C-mutated metastatic colorectal cancer, despite higher response rates. In upper GI cancers, HERIZON-GEA-01 supported zanidatamab-based treatment with maintained quality of life, while STAR-221 did not show added benefit from TIGIT inhibition over nivolumab plus chemotherapy.
More details are available in the official ESMO Gastrointestinal Cancers Congress 2026 programme.
Written by Noha Fouad Rashad, MD, Lecturer of Medical Oncology, Suez University, Egypt