How Will Gastrointestinal Cancer Standards of Care Change? An ESMO Recap

Following a fruitful European Society of Medical Oncology (ESMO) Congress 2025 for gastrointestinal malignancies, CancerNetwork® organized an X Spaces discussion hosted by 3 experts. They were Nicholas J. Hornstein, MD, an assistant professor at the Donald and Barbara Zucker School of Medicine of Hofstra University and Northwell Health; Timothy Brown, MD, an assistant professor in the Department of Internal Medicine and the associate program director of the Hematology & Oncology Fellowship at UT Southwestern Medical Center; and Udhayvir S. Grewal, MD, an assistant professor in the Department of Hematology and Medical Oncology at Emory University School of Medicine.

Each doctor focused on a specific disease type, highlighting the most important abstracts in colorectal cancer, pancreatic neuroendocrine tumors (NETs), and upper gastrointestinal cancers.

The Phase 3 MATTERHORN Trial (NCT04592913)

Results from MATTERHORN demonstrated that adding durvalumab (Imfinzi) to 5-fluorouracil, leucovorin (folinic acid), oxaliplatin, and docetaxel (FLOT) improved overall survival (OS) compared with FLOT plus placebo in patients with resectable gastric/gastroesophageal junction (GEJ) adenocarcinoma, regardless of pathological status.¹

In the intention-to-treat population, the median OS was not reached in either arm, and the hazard ratio (HR) was 0.78 (95% CI, 0.63-0.96; P = .021). Notably, the improvement was observed regardless of PD-L1 status; in patients with PD-L1–positive disease, the HR was 0.79 (95% CI, 0.63-0.99), and in patients with PD-L1–negative disease, the HR was 0.79 (95% CI, 0.41-1.50).

“This, I believe, will seal durvalumab plus FLOT as the standard of care for resectable [gastric/GEJ] cancers,” said Brown.

The Observational ASPEN Study (NCT03084770)

The ASPEN study showed that active surveillance was a safe approach for patients with low-grade, asymptomatic, nonfunctioning pancreatic neuroendocrine tumors (NETs) fewer than 2 centimeters in size.²

Of the 1000 patients enrolled in the trial, 20 patients died, of whom 18 underwent active surveillance and 2 underwent surgery. Nineteen of the deaths were unrelated to pancreatic NETs; 1 death in the surgery arm was related to a pancreatic NET. After surgery, 5 patients had disease relapse or progression. With a median follow-up of 42 months (IQR, 25-60), the OS analysis showed a P value of 0.530.

“This really settles the debate on whether or not to surgically operate on patients with a [pancreatic NET] size of [fewer] than 2 centimeters and shows that active surveillance is a safe option for these patients with pancreatic NETs [fewer] than 2 centimeters in size and non-functional NETs,” said Grewal.

Data From the Phase 2/3 FOxTROT (NCT00647530) and Phase 2 NICHE-2 (NCT03026140) Trials

Neoadjuvant nivolumab (Opdivo) plus ipilimumab (Yervoy) achieved a clinically meaningful and statistically significant improvement in long-term outcomes, including responses and survival, compared with chemotherapy strategies in patients with mismatch repair deficient (dMMR) or microsatellite instability–high (MSI-H) locally advanced colon cancer.³

In NICHE-2, neoadjuvant nivolumab plus ipilimumab achieved a 3-year disease-free survival (DFS) rate of 100% compared with 80% (95% CI, 73%-85%) with all chemotherapy strategies in FOxTROT (P <.001). Nivolumab plus ipilimumab maintained a 100% DFS rate in patients with clinical stage T3 and T4 disease in NICHE-2, whereas FOxTROT achieved DFS rates of 84% (95% CI, 76%-90%) and 70% (95% CI, 58%-80%), respectively (P <.001).

Additionally, nivolumab plus ipilimumab achieved a pathologic complete response (pCR) rate of 72.3%, with a pathologic partial response (pPR) rate of 25.5% and no response in 1.1%. Chemotherapy achieved a pCR rate of 4.3%, a pathologic pPR rate of 2.6%, and a mild to no response rate of 91.4%.

“Overnight, this should change the standard of care, even if the FDA hasn’t caught on yet, at least from my perspective. If I find out about a [patient with] MSI-H disease before they go to the [operating room], I’m probably running [to give them ipilimumab plus nivolumab],” said Hornstein.

References

1. Tabernero J, Al-Batran S-E, Wainberg ZA, et al. Final overall survival (OS) and the association of pathological outcomes with event-free survival (EFS) in MATTERHORN: a randomised, phase III study of durvalumab (D) plus 5-fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) in resectable gastric / gastroesophageal junction (G / GEJ) adenocarcinoma. Presented at: ESMO 2025 Congress; October 17–21, 2025; Berlin, Germany. Abstract LBA81.
2. Partelli S, Andreasi V, Zerbi A, et al. Management of asymptomatic sporadic nonfunctioning pancreatic neuroendocrine neoplasms ≤2 cm: a prospective international observational multicentric cohort study ASPEN study. Presented at: ESMO 2025 Congress; October 17–21, 2025; Berlin, Germany. Abstract LBA36.
3. Seligmann J, van den Dungen LDW, Balduzzi S, et al. Comparison of outcomes in clinical trials of locally advanced dMMR colon cancer: data from the FOxTROT and NICHE-2 trials. Presented at: ESMO 2025 Congress; October 17–21, 2025; Berlin, Germany. Abstract 7240.