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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.

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; 

= .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.

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 

“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.

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 (

<.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 (

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.

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.

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.

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.

European Society for Medical Oncology Congress (ESMO)

Three GI cancer medical oncologists discuss the most significant abstracts in GI cancers from the 2025 ESMO Congress.

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

, Benjamin Golas, MD, spoke about the current treatment landscape for patients with peritoneal carcinomatosis, discussing how the use of pressurized intraperitoneal aerosolized chemotherapy (PIPAC) may offer improvements in clinical outcomes.

Golas is the chief of Surgical Oncology of the Central Region for Hackensack Meridian Health.

According to Golas, standard therapeutic approaches include combining cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC), which may cause collateral damage to healthy tissue while eliciting toxicities such as nausea, vomiting, and bone marrow suppression. Additionally, certain surgical procedures may last up to 14 hours and confer an extensive morbidity profile, thereby increasing complication rates.

Golas described how PIPAC, a minimally invasive laparoscopic technique, may help avoid pain and other adverse effects associated with surgery while facilitating more direct delivery of chemotherapy in the peritoneal cavity. He noted that treatment with PIPAC typically takes 45 minutes to an hour, allowing some patients to return home on the same day of the procedure.

Although clinicians are still learning the correct indications for PIPAC, Golas stated that any patient with peritoneal carcinomatosis should be a candidate to receive treatment with this strategy. Furthermore, he described how the next steps for improving outcomes in this population include finding new ways to incorporate PIPAC into more extensive treatment plans for patients.

“PIPAC is a new treatment and a new potential option that doesn't replace systemic chemotherapy, but I do think it can work in conjunction with systemic chemotherapy. We can offer this bimodal approach where we're directly treating the peritoneal disease and offering [intravenous] chemotherapy,” Golas stated. “We clearly have a long way to go in terms of clinical trials and learning what the best ways are to use this. But there are patients out there who will benefit from that, so I think referral to a center that focuses and has expertise in PIPAC for patients with peritoneal carcinomatosis is critical.”

Benjamin Golas, MD, discusses how the use of PIPAC may work in conjunction with systemic chemotherapy for those with peritoneal carcinomatosis.

Harnessing PIPAC to Improve Outcomes in Peritoneal Carcinomatosis

FDA approval of sotorasib (Lumakras) plus panitumumab (Vectibix),

 and how it may affect the treatment paradigm for patients with 

G12C-mutant metastatic colorectal cancer (CRC).

Fakih is a professor in the Department of Medical Oncology & Therapeutics Research, associate director for Clinical Sciences, medical director of the Briskin Center for Clinical Research, division chief of GI Medical Oncology, and co-director of the Gastrointestinal Cancer Program at City of Hope Comprehensive Cancer Center in Duarte, California.

According to Fakih, the approval of this combination regimen is a “welcome step” for those with metastatic CRC harboring 

G12C mutations. Based on supporting data from the phase 3 CodeBreaK 300 trial (NCT05198934), sotorasib/panitumumab may prolong progression-free survival (PFS) and reduce disease burden in patients while offering improvements in other outcomes vs prior standards of care (SOC) like trifluridine/tipiracil (Lonsurf) and regorafenib (Stivarga).

Topline data at the time of the approval showed a median PFS of 5.6 months (95% CI, 4.2-6.3) with sotorasib at 960 mg plus panitumumab vs 2.0 months (95% CI, 1.9-3.9) in the SOC arm, in which patients were assigned to receive trifluridine/tipiracil or regorafenib (HR, 0.48; 95% CI, 0.30-0.78; 

= .005). Additionally, the overall response rate was 26% (95% CI, 15%-40%) vs 0% (95% CI, 0%-7%) in each respective arm.

Looking ahead, Fakih highlighted the potential next steps for research associated with the sotorasib combination as well as other novel therapeutic strategies in the gastrointestinal cancer space. For example, he described the phase 3 CodeBreaK 301 study (NCT06252649), which will evaluate sotorasib/panitumumab as frontline therapy when administered in combination with folinic acid, fluorouracil, and irinotecan (FOLFIRI) vs FOLFIRI plus bevacizumab (Avastin) in metastatic 

Other novel agents under development in the space include RAS inhibitors and immunotherapy regimens combining CTLA-4 inhibitors with anti–PD-L1 agents.

FDA approves sotorasib with panitumumab for KRAS G12C-mutated colorectal cancer. News release. FDA. January 16, 2025. Accessed February 12, 2025. https://shorturl.at/1WviB

Kim TW, Price T, Grasselli J, et al. A phase 3 study of first-line sotorasib, panitumumab, and FOLFIRI versus FOLFIRI with or without bevacizumab-awwb for patients with KRAS G12C–mutated metastatic colorectal cancer (CodeBreaK 301).

 2025;43(suppl 4):TPS326. doi:10.1200/JCO.2025.43.4_suppl.TPS326

The approval of sotorasib plus panitumumab is a “welcome step” in KRAS G12C-mutated colorectal cancer, according to Marwan G. Fakih, MD.

Sotorasib Combo Approval May Address Novel Therapy Need in KRAS G12C+ CRC

 sat down with Kelley A. Rone, DNP, RN, AGNP-c, to discuss the importance of speaking compassionately and ensuring patient awareness when leading end-of-life discussions among those with gastrointestinal (GI) cancers. The discussion also focused on combating burnout in the clinic, using opioids to help manage pain and other symptoms, and educating all members of a multidisciplinary team on initiating end-of-life conversations with their patients.

Rone is an advanced practice nurse (APN) in GI oncology at the Mayo Clinic in Phoenix, Arizona.

As part of leading these end-of-life conversations, Rone emphasized the necessity of addressing the discomfort patients tend to feel when talking about the fact that they may die from their cancer. Speaking with these patients may involve being open about the possibility of terminating therapy early if treatment-related toxicity such as fevers, diarrhea, and pain outweigh any potential efficacy or diminish quality of life. Additionally, Rone highlighted how APNs may be more comfortable with speaking about death than other team members.

Rone also discussed the importance of managing fatigue and pain as patients near the end of their lives. In her role, she initiates education on pain management early in end-of-life care discussions to make patients feel more comfortable about receiving opioids for symptoms.

When working with other members of a multidisciplinary care team, Rone illustrated the challenge of having physicians understand that their treatments may fail in younger patients and helping other oncologists become more experienced in speaking about death with patients. Regarding the idea of mitigating burnout and maintaining one’s mental well-being, Rone described how her role has given her perspective on what is truly important about life.

“This [role] helps you appreciate the finality of life. You don’t get upset about [minor] things after you see a 39-year-old with metastatic cancer,” Rone stated. “You learn to have an appreciation for the good things and not dwell so much on the bad things.”

Kelley A. Rone, DNP, RN, AGNP-c, provides perspective on approaching end-of-life conversations with patients with GI cancers.

Educating Patients and Clinicians on End-of-Life Care and Discussions

2024 Society of Surgical Oncology Annual Meeting (SSO), 

 spoke with a variety of surgical oncology experts regarding the topline data they presented. Each conversation also expanded upon how these results can be implemented into the clinical space and the next research steps.

, a complex general surgical oncology fellow at Moffitt Cancer Center, discussed findings from her presentation highlighting responses to neoadjuvant immune checkpoint inhibitors among select patients with mismatch repair deficient (dMMR) gastroesophageal cancer.

Looking ahead, Shannon described her aim to optimize treatment strategies for this patient population, which may include assessing whether single-agent treatment can be efficacious while avoiding toxicity associated with combination regimens.

, an associate member in the Gastrointestinal Department, section leader for Peritoneal Disease, and the program director for the Complex General Surgical Oncology Fellowship at Moffitt Cancer Center, spoke about his session, which was aimed at determining appropriate conditions for using cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (HIPEC) for those with colorectal cancer (CRC) and peritoneal metastases.

Dineen highlighted that there is “good evidence” in support of HIPEC as a “valid treatment option” and emphasized the need to encourage medical oncologists to refer patients for consideration of surgery. Additionally, he spoke about other advancements he hopes to see in this patient population, including the development of markers of various disease volumes that can help identify potential recurrence in those who receive surgery.

, a research fellow in the Department of Surgical Oncology at City of Hope National Medical Center in Duarte, California, detailed findings from a retrospective analysis indicating disparate treatment access and cancer-related mortality based on racial-economic segregation.

Specifically, data showed that those who lived in Black and poor majority areas were less likely to receive care that was in accordance with various treatment guidelines while having worse overall survival outcomes. Regarding the next steps, Waheed described his intentions of sharing his findings with policymakers who may create legislature intended to mitigate the disparities observed in the analysis.

Shannon AB, Mehta RJ, Mok SR, et al. Pathologic response to neoadjuvant immunotherapy in DNA mismatch repair protein-deficient gastroesophageal cancers. Presented at the Society of Surgical Oncology 2024 Annual Meeting; March 20-23, 2024; Atlanta, GA. Abstract 94.

Dineen S. Optimal tumor burden for CRS/HIPEC in colorectal cancer. Presented at the Society of Surgical Oncology 2024 Annual Meeting; March 20-23, 2024; Atlanta, GA.

Waheed MT, Sullivan KM, Haye S, et al. Impact of racialized residential segregation on guideline concordant cancer care and survival. Presented at the Society of Surgical Oncology (SSO) 2024 Annual Meeting; March 20 – 23, 2024; Atlanta, GA; abstract E126.

Experts discuss findings related to gastrointestinal cancer outcomes as well as treatment inequalities presented at the 2024 SSO Annual Meeting.

Surgeons Talk Key Treatment and Institutional Advances Across Oncology Care

 Jun Gong, MD, and Daneng Li, MD, sat down to discuss the most relevant trial data to have come from the conference. They convened for a live X Space hosted by CancerNetwork

During the discussion, they covered different trials across the gastrointestinal space, which included those evaluating different disease states from hepatocellular carcinoma (HCC) to colorectal cancer (CRC), and those assessing circulating tumor DNA (ctDNA) dynamics.

Gong, a hematologic oncologist focusing on gastrointestinal and genitourinary cancers at Cedars-Sinai Medical Center, and Li, an associate professor in the Department of Medical Oncology and Therapeutics Research at City of Hope, each gave their perspective on the clinical trial data and discussed if they had implemented any of these study treatments into clinical practice.

Investigated lutetium Lu 177 dotatate (Lutathera) plus octreotide vs octreotide alone for advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs).

Lutetium Lu 177 significantly improved progression-free survival (PFS) and overall response rate (ORR) compared with octreotide alone.

The agent may be considered for patients with high-grade GEP-NETs who desire significant tumor shrinkage.

Studied transarterial chemoembolization (TACE) plus durvalumab (Imfinzi) with or without bevacizumab (Avastin) for unresectable HCC.

Durvalumab/bevacizumab plus TACE improved PFS compared with placebo plus TACE.

TACE may be preferred over transarterial radioembolization (TARE) due to faster patient recovery.

Evaluated nivolumab (Opdivo) plus ipilimumab (Yervoy) vs chemotherapy for first-line treatment of microsatellite instability-high/mismatch repair deficient metastatic CRC.

Nivolumab/ipilimumab demonstrated superior PFS compared with chemotherapy.

Chemotherapy may no longer be the standard first-line treatment for this patient population.

Assessed the impact of minimal residual disease (MRD) detected by ctDNA on disease recurrence in patients with stage II and III CRC receiving adjuvant chemotherapy.

MRD positivity was associated with worse disease-free survival (DFS).

ctDNA clearance at 12 weeks indicated improved DFS.

ctDNA is a promising biomarker that can be used to predict recurrence in patients with CRC.

Patients with ctDNA-positive disease had a worse DFS than patients with ctDNA-negative disease.

This suggests that ctDNA may be useful for making treatment decisions, but more research is needed before it can be used in clinical practice.

Fruquintinib (Fruzaqla) improved the quality of life in patients with metastatic CRC when combined with best supportive care and significantly improved quality-adjusted time without symptoms of disease or toxicity compared with placebo and best supportive care.

The study showed positive effects on PFS, response rate, disease control, and duration of response with the fruquintinib combination.

the FDA approval of fruquintinib for metastatic CRC

Singh S, Halperin D, Myrehaug S, et al. [177Lu]Lu-DOTA-TATE in newly diagnosed patients with advanced grade 2 and grade 3, well-differentiated gastroenteropancreatic neuroendocrine tumors: primary analysis of the phase 3 randomized NETTER-2 study. 

. 2024(suppl 3):LBA588. doi:10.1200/JCO.2024.42.3_suppl.LBA588

Lencioni R, Kudo M, Erinjeri J, et al. EMERALD-1: a phase 3, randomized, placebo-controlled study of transarterial chemoembolization combined with durvalumab with or without bevacizumab in participants with unresectable hepatocellular carcinoma eligible for embolization. 

. 2024;42(suppl 3):LBA432. doi.10.1200/JCO.2024.42.3_suppl.LBA432

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. 

. 2024;42(suppl_3):LBA768. doi.10.1200/JCO.2024.42.3_suppl.LBA768

Kasi P, Aushev V, Ensor J, et al. Circulating tumor DNA (ctDNA) for informing adjuvant chemotherapy (ACT) in stage II/III colorectal cancer (CRC): interim analysis of BESPOKE CRC study. 

. 2024;42 (suppl _3):9. doi:10.1200/JCO.2024.42.3_suppl.9

Yukami H, Nakamura Y, Mishima S, et al. Circulating tumor DNA (ctDNA) dynamics in patients with colorectal cancer (CRC) with molecular residual disease: Updated analysis from GALAXY study in the CIRCULATE-JAPAN. 

. 2024;42(suppl_3):6. doi:10.1200/JCO.2024.42.3_suppl.6

Stintzing S, Tabernero J, Satoh T, et al. Quality-adjusted time without symptoms of disease or toxicity (Q-TWiST) analysis of fruquintinib + best supportive care (BSC) compared with placebo + BSC in metastatic colorectal cancer (mCRC): results from the FRESCO-2 trial. 

. 2024;42(suppl 3):116. doi:10.1200/JCO.2024.42.3_suppl.116

FDA approves fruquintinib in refractory metastatic colorectal cancer. FDA. News release. November 8, 2023. Accessed February 7, 2024. https://shorturl.at/isJW2

ASCO Gastrointestinal Cancer Symposium

Jun Gong, MD, and Daneng Li, MD, spoke about trials they feel can impact the gastrointestinal space during a CancerNetwork® X Space.

Gastrointestinal Cancer

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