Top 5 Takeaways for Gastrointestinal Cancer Management From 2025 ASCO GI

Findings from the phase 3 CheckMate 8HW trial (NCT04008030) demonstrated a clinically meaningful and statistically significant improvement in progression-free survival (PFS) when administering nivolumab (Opdivo) in combination with ipilimumab (Yervoy) for patients with metastatic colorectal cancer (CRC) and mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H) disease.

The 2025 ASCO Gastrointestinal Cancers Symposium revealed key updates in the development and research of various treatment regimens that may demonstrate clinical utility across a wide range of gastrointestinal (GI) cancer populations. As part of several oral presentations, late-breaking abstracts, and poster sessions, experts highlighted how different immuno-oncology agents, chemotherapeutic strategies, and radiation modalities may affect the treatment paradigm.

CancerNetwork^® covered the latest findings reported from these presentations. Here are the top 5 articles on potentially impactful data from this year’s symposium.

#1: Nivolumab/Ipilimumab Extends PFS in MSI-H/dMMR Metastatic Colorectal Cancer

Findings from the phase 3 CheckMate 8HW trial (NCT04008030) demonstrated a clinically meaningful and statistically significant improvement in progression-free survival (PFS) when administering nivolumab (Opdivo) in combination with ipilimumab (Yervoy) for patients with metastatic colorectal cancer (CRC) and mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H) disease.¹

The median PFS in the MSI-H or dMMR population was not reached (95% CI, 53.8 months to not evaluable [NE]) in the nivolumab/ipilimumab arm and 39.3 months (95% CI, 22.1-NE) in the nivolumab monotherapy arm. In each respective arm, the 12-month PFS rates were 76% vs 63%, the 24-month rates were 71% vs 56%, and the 36-month rates were 68% vs 51%. Subgroup analysis data showed that the combination regimen improved PFS across all lines of therapy in prespecified groups based on characteristics like ECOG performance status, sex, and liver metastases.

“These results, combined with the previously reported superior PFS with nivolumab/ipilimumab vs chemotherapy in the first-line setting,² establish nivolumab plus ipilimumab as a new standard of care for patients with MSI-H/dMMR metastatic [CRC],” Thierry André, MD, a professor of medical oncology at the Sorbonne Université in Paris and head of the Medical Oncology Department at the Saint Antoine Hospital, Assistance Publique Hôpitaux de Paris, France, stated regarding these findings.¹

#2: Sintilimab Plus CRT Yields Superior Responses in Resectable, Locally Advanced ESCC

Adding sintilimab (Tyvyt) to neoadjuvant chemoradiotherapy (CRT) produced a higher pathological complete response (pCR) rate vs CRT alone among patients with resectable locally advanced esophageal squamous cell carcinoma (ESCC) in the phase 3 SCIENCE trial (NCT05244798).³

Sintilimab/CRT yielded a pCR rate of 60.0% (95% CI, 44.3%-74.3%) vs 13% (95% CI, 4.9%-26.3%) using sintilimab plus chemotherapy and 47.3% (95% CI, 33.7%-61.2%) with CRT alone.

“Adding sintilimab…to neoadjuvant CRT may improve the pathological outcomes without increasing surgical risks. Neoadjuvant CRT combined with [immunotherapy] has the potential to become the new standard of care [SOC],” Xuefeng Leng, MD, PhD, of the Department of Thoracic Surgery at Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, said in a presentation of these results.³

#3: TACE Plus Camrelizumab/Rivoceranib Extends PFS in Unresectable Liver Cancer

A presentation on the phase 2 CARES-005 study (NCT04559607) showed a clinically meaningful and statistically significant PFS improvement with transarterial chemoembolization (TACE) plus camrelizumab and rivoceranib (apatinib) among those with unresectable hepatocellular carcinoma (HCC).⁴

Across the intent-to-treat (ITT) population, TACE plus camrelizumab/rivoceranib elicited a median PFS of 10.8 months (95% CI, 8.8-13.7) per Response Evaluation Criteria in Cancer of the Liver (RECICL) criteria vs 3.2 months (95% CI, 2.4-4.2) using TACE alone (HR, 0.34; 95% CI, 0.24-0.50; P <.0001). Regardless of factors such as age, sex, and prior exposure to TACE, the addition of camrelizumab/rivoceranib to TACE appeared to prolong PFS across patient subgroups.

On top of the PFS improvement, study author Gao-Jun Teng, MD, of Zhongda Hospital, Southeast University, noted that the safety profile of the experimental regimen in the CARES-005 study “was manageable and consistent with the known adverse effect [AE] profiles of TACE, camrelizumab, and rivoceranib in unresectable HCC.”⁴

#4: SCRT Followed by Cadonilimab/Chemo Shows Responses in pMMR/MSS Rectal Cancer

According to data from the phase 2 NeoCaCRT trial (NCT05792735), promising pCRs and manageable toxicity occurred when combining short-course radiotherapy (SCRT) with cadonilimab (AK104) and chemotherapy for patients with mismatch repair proficient (pMMR) or microsatellite stable (MSS) locally advanced rectal cancer (LARC).⁵

Study treatment produced a pCR rate of 37.0% (95% CI, 19.4%-57.6%), a clinical major pathological response rate (MPR) of 55.6% (95% CI, 35.3%-74.5%), and a clinical CR rate of 22.2% (95% CI, 8.6%-42.2%). Any-grade and grade 3/4 treatment-related AEs affected 88.9% and 22.2% of patients, respectively, with the most common toxicities including diarrhea (37%), nausea (37%), fatigue (37%), and neutropenia (26%).

“In patients with pMMR/MSS LARC, neoadjuvant SCRT with cadonilimab plus [chemotherapy] resulted in promising pCR rates with a manageable safety profile. These data deserve further investigations in a phase 3 randomized trial,” lead study author Wan He, a researcher in the Department of Oncology at Shenzhen People’s Hospital in Shenzhen, China, wrote in the poster with coinvestigators.⁵

#5: T-DM1 Shows Promise in HER2+ Biliary Tract Cancer

In a phase 2 trial (CTRI/2023/07/055785), ado-trastuzumab emtansine (T-DM1; Kadcyla) appeared to be well tolerated among patients with HER2-positive biliary tract cancer (BTC). Although PFS did not appear to statistically improve with T-DM1 compared with historical data, select outcomes in certain patients may warrant additional research.

The median PFS was 3.1 months (95% CI, 2.3-3.8), and the 3-month PFS rate was 51.2% (95% CI, 33.4%-69.0%). Additionally, treatment yielded a median overall survival (OS) of 7.1 months (95% CI, 5.1-9.1) and an OS rate of 56.5% at 6 months.

Among patients who did not experience rapid progression on prior lines of treatment, T-DM1 produced a median PFS of 4.9 months (95% CI, 2.9-6.9) and a 3-month rate of 70% (95% CI, 44.8%-95.2%).

“Patients who did not have rapid progression on prior systemic therapy appeared to have a more favorable survival in comparison with rapid progressors and the role of T-DM1 in such favorable cohorts can be expected in larger studies,” Vikas Ostwal, MD, a professor at Tata Memorial Care in Mumbai, wrote with coauthors.⁶

References

1. Andre T, Elez E, Lenz H-J, et al. First results of nivolumab (NIVO) plus ipilimumab (IPI) vs NIVO monotherapy for microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC) from CheckMate 8HW. J Clin Oncol. 2025;43(suppl 4):LBA143. doi:10.1200/JCO.2025.43.4_suppl.LBA143
2. Andre T, Elez E, Van Cutsem E, et al. Nivolumab (NIVO) plus ipilimumab (IPI) vs chemotherapy (chemo) as first-line (1L) treatment for microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC): First results of the CheckMate 8HW study. J Clin Oncol. 2024;42(suppl 3):LBA768. doi:10.1200/JCO.2024.42.3_suppl.LBA768
3. Leng X, He W, Lyu J, et al. Preliminary results from the multicenter, randomized phase III trial (SCIENCE): Comparing chemotherapy plus sintilimab and chemoradiotherapy plus sintilimab versus chemoradiotherapy for neoadjuvant treatment in resectable locally advanced esophageal squamous cell carcinoma. J Clin Oncol. 2025;43(suppl 4):LBA329. doi:10.1200/JCO.2025.43.4_suppl.LBA329
4. Zhu H, Teng G-J, Fan W, et al. Transarterial chemoembolization (TACE) combined with camrelizumab and apatinib versus TACE alone in the treatment of unresectable hepatocellular carcinoma eligible for embolization: A multicenter, open-label, randomized, phase 2 study (CAP-ACE). J Clin Oncol. 2025;43(suppl 4):LBA522. doi:10.1200/JCO.2025.43.4_suppl.LBA522
5. He W, Huang J, Liao G, et al. Short-course radiation (SCRT) followed by 6 cycles of cadonilimab plus mFOLFOX6 as neoadjuvant therapy for patients with locally advanced rectal cancer (LARC): A multicenter, single arm phase 2 trial (NeoCaCRT). J Clin Oncol. 2025;43(4):LBA210. doi:10.1200/JCO.2025.43.4_suppl.LBA210
6. Ostwal VS, Bhargava PG, Kushal RK, et al. Trastuzumab emtansine as second-line therapy in HER2 positive advanced biliary tract cancers: Single arm prospective phase II clinical trial (TAB-3 trial). J Clin Oncol. 2025;43(4):584. doi:10.1200/JCO.2025.43.4_suppl.584