4 Key Abstracts from the 2026 ASCO Gastrointestinal Cancers Symposium

Rachna Shroff, MD, MS, FASCO University of Arizona | Rahul Gosain, MD, MBA Wilmot Cancer Institute | Rohit Gosain, MD Roswell Park Comprehensive Cancer Center

Key Points

• A MATTERHORN analysis showed perioperative durvalumab did not negatively affect surgical outcomes in resectable gastric or gastroesophageal junction (GEJ) adenocarcinomas.

• Zanidatamab plus tislelizumab and chemotherapy is set to become the new standard of care in HER2–positive metastatic gastric or GEJ cancer based on HERIZON-GEA-01.

• Further BREAKWATER data found encorafenib and cetuximab improved outcomes for metastatic colorectal cancer (mCRC) regardless of the chemotherapy backbone used.

• The COMMIT trial supports progression-free survival (PFS) benefit with atezolizumab plus chemotherapy and bevacizumab, although the value is uncertain given strong data for dual checkpoint inhibitor regimens in mCRC.

2026 ASCO Gastrointestinal Cancers Symposium 

Cohosts of the Oncology Brothers podcast, Rahul Gosain, MD, MBA, of Wilmot Cancer Institute, and Rohit Gosain, MD, of Roswell Park Comprehensive Cancer Center, invited Rachna Shroff, MD, MS, FASCO, of University of Arizona Cancer Center, to discuss data presented at the 2026 ASCO Gastrointestinal Cancers Symposium (ASCO GI) from four key upper gastrointestinal and colorectal cancer trials: MATTERHORN, HERIZON-GEA-01, BREAKWATER, and COMMIT. 

Durvalumab and Surgical Outcomes in MATTERHORN

In November 2025, the FDA approved perioperative durvalumab plus FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) for resectable gastric or GEJ adenocarcinoma. Perioperative durvalumab is now standard of care for all patients, regardless of PD-L1 status. The ASCO GI presentation described surgery outcomes and characteristics among MATTERHORN participants.

For patients in the durvalumab arm compared with the control arm, 90.9% versus 90.3% attempted surgery, 10.1% versus 10.8% had a surgery delay, and 86.9% versus 84.4% completed surgery, respectively. The most common surgery delay was less than 2 weeks in both arms. After surgery, 2.3% of patients in the durvalumab arm versus 4.6% in the control arm had an adjuvant treatment delay. In patients who completed surgery, durvalumab improved event-free survival regardless of tumor location, resection margin, or lymphadenectomy type. 

These data reassure that the addition of durvalumab does not negatively affect completion of surgery or surgical adverse events in resectable gastric or GEJ cancers, said Dr. Shroff.

HERIZON-GEA-01 Data From ASCO GI 2026

The HERIZON-GEA-01 trial evaluated zanidatamab with or without tislelizumab plus chemotherapy versus trastuzumab plus chemotherapy as first-line treatment for patients with HER2–positive metastatic gastric or GEJ adenocarcinoma. In the first interim analysis, zanidatamab plus tislelizumab and chemotherapy significantly improved median PFS at 12.4 months (95% CI, 9.8-18.5) versus 8.1 months (95% CI, 7.0-8.9) with control (HR, 0.63; 95% CI, 0.51-0.78; P < .0001). The zanidatamab triplet also significantly improved median overall survival (OS) at 26.4 months (95% CI, 21.5-30.3) versus 19.2 months (95% CI, 16.8-21.8) with control (HR, 0.72; 95% CI, 0.57-0.90; P = .0043). In the second experimental arm, zanidatamab plus chemotherapy significantly improved PFS and numerically improved OS versus control. 

After initiation of HERIZON-GEA-01, trastuzumab plus chemotherapy standard of care was updated to include pembrolizumab based on the KEYNOTE-811 trial. While the control arm in HERIZON-GEA-01 did not reflect this change, the unprecedented median OS reported with the zanidatamab triplet will likely lead to its approval as the new standard of care for metastatic gastric or GEJ adenocarcinoma, said Dr. Shroff. In a broader sense, HERIZON-GEA-01 established zanidatamab as the new standard for HER2–targeted agents across disease sites, she added.

BREAKWATER Update Confirms Encorafenib/Cetuximab in mCRC

Previous analyses from the phase 3 BREAKWATER trial established encorafenib and cetuximab plus FOLFOX (leucovorin, fluorouracil, and oxaliplatin) improved outcomes compared with control in first-line treatment for patients with BRAF V600E–mutated mCRC. At ASCO GI, authors presented the primary analysis from cohort 3 of BREAKWATER on encorafenib and cetuximab plus FOLFIRI (leucovorin, fluorouracil, and irinotecan) versus FOLFIRI with or without bevacizumab.

The objective response rate (ORR) was 64.4% with encorafenib and cetuximab plus FOLFIRI compared with 39.2% with control (odds ratio [OR], 2.76; 95% CI, 1.42-5.35; P = .001). The estimated median duration of response was not estimable (NE;95% CI, NE-NE) in cohort 3 and NE (95% CI, 7.0-NE) in the control cohort. Among responders, 57.4% in cohort 3 versus 34.5% in the control cohort had responses lasting 6 or more months. The median time to response was 6.9 weeks (range, 5.4-36.1) in cohort 3 versus 7.1 weeks (range, 5.9-25.3) in the control cohort. The median OS was NE (95% CI, NE-NE) in cohort 3 and NE (95% CI, 12.1-NE) in the control (HR, 0.49; 95% CI, 0.24-1.03).

Results from BREAKWATER cohort 3 showed that encorafenib plus cetuximab is a crucial regimen for patients with BRAF V600E–mutated mCRC, while the chemotherapy backbone used in combination can be alternated, Dr. Shroff said. 

Chemotherapy Plus Atezolizumab Improves mCRC Outcomes in COMMIT

The phase 3 COMMIT trial compared atezolizumab monotherapy with FOLFOX, bevacizumab, and atezolizumab as frontline treatment for patients with microsatellite instability-high (MSI-H) and DNA mismatch repair deficient (dMMR) mCRC. COMMIT initially included a third arm of FOLFOX and bevacizumab alone, but the arm was closed after results from the KEYNOTE 177 trial were published. COMMIT enrolled 41 patients each to the atezolizumab and FOLFOX, bevacizumab, and atezolizumab arms. Authors presented an interim analysis of PFS, ORR, and disease control rate (DCR) outcomes for each arm after a median follow-up of 3.5 years.

	FOLFOX, bevacizumab, and atezolizumab	Atezolizumab
Median PFS	24.5 months (95% CI, 10.1-NE)	5.3 months (95% CI, 2.2-18.2)
12-month PFS	66.7%	35.1%
24-month PFS	53.7%	31.6%
ORR	86.1%	46%
12-month DCR	64.7%	32.4%

Notably, patient accrual in COMMIT was suspended after results from the CheckMate 8HW trial showed a substantial PFS benefit with frontline ipilimumab plus nivolumab in MSI-H, dMMR mCRC. While the survival outcomes with ipilimumab plus nivolumab are hard to ignore, the tolerability of dual checkpoint inhibition is a potential limiting factor, and treatment decisions for this population may come down to which individual patients may require more aggressive disease control, said Dr. Shroff.