Oncologists Highlight Key Takeaways and Abstracts From the 2025 ESMO GI Cancers Congress

Eileen M. O'Reilly, MD

The 2025 ESMO Gastrointestinal (GI) Cancers Congress delivered clinically meaningful data across GI cancer types, highlighting advances in immunotherapy, targeted therapy, and combination strategies. From late-breaking data in colorectal cancer (CRC) and hepatocellular carcinoma (HCC) to early-phase trials in rectal and gastric cancers, expert discussions explored key developments in RAS-targeted therapy for pancreatic cancer, HER2-directed treatment in cholangiocarcinoma, novel combinations in hepatobiliary and esophagogastric malignancies, and more.

OncLive® spoke with leading investigators throughout the meeting to capture their insights on the most relevant findings and how they may inform future clinical practice and ongoing research efforts. Read on see insights from:

• Eileen M. O’Reilly, MD, the Winthrop Rockefeller Endowed Chair in Medical Oncology, associate director for clinical research, and co-director of the Center for Pancreatic Cancer Research at Memorial Sloan Kettering Cancer Center in New York, New York
• Rocío García-Carbonero, MD, PhD, head of the Gastrointestinal Tumors Section in the Department of Medical Oncology at Hospital Universitario 12 de Octubre in Madrid, Spain, and associate professor of oncology at Universidad Complutense de Madrid
• Elena Elez, MD, a medical oncologist in the Gastrointestinal and Endocrine Tumors Unit and principal investigator of the Colorectal Cancer and Precision Oncology Program at Vall d’Hebron Institute of Oncology (VHIO) in Barcelona, Spain
• Zev A. Wainberg, MD, professor of medicine in the Division of Hematology/Oncology and co-director of the GI Oncology Program at UCLA Health in Los Angeles, California
• Masatoshi Kudo, MD, professor and chairman of the Department of Gastroenterology and Hepatology at Kindai University Faculty of Medicine in Osaka, Japan
• Connie Lai, MD, Resident Medical Oncologist at Queen Elizabeth Hospital in Hong Kong, China
• Kohei Shitara, MD, chief of the Department of Gastrointestinal Oncology at the National Cancer Center Hospital East in Kashiwa, Japan
• Sanjiv Gangaram-Panday, MD, a medical oncologist in the Department of Gastrointestinal Oncology at Netherlands Cancer Institute in Amsterdam, Netherlands

Pancreatic Cancer

O'Reilly:It’s always invigorating and inspiring to come, listen, and see where the field is moving—not just in pancreatic cancer, but in GI cancers in general. What’s on the very proximate horizon in pancreatic cancer is the RAS story. There has been a lot of discussion about biology, the importance of RAS [mutation testing] in pancreatic cancer, how to test, [and] when to test.

There were also discussions about ongoing randomized trials. In the second-line setting, the [phase 3] RASolute 302 trial [NCT06625320] is comparing daraxonrasib [RMC-6236], which is a pan-RAS oral inhibitor, with chemotherapy in a large patient population. That study is actively accruing patients [with previously treated metastatic pancreatic ductal adenocarcinoma] across the world and will hopefully complete accrual shortly. [Data are] expected to read out in 2026, and there’s high potential for [this study] to inform practice [and] to change how we approach this disease.

In parallel with all of that: [How do we] bring these drugs into [earlier settings if they are successful], such as locally advanced [pancreatic cancer] and the adjuvant/neoadjuvant settings? It’s encouraging to now have a couple of [positive studies] and a few [potentially positive studies] in the future.

CRC

García-Carbonero: There were other studies…presented [at the congress] that were very relevant. For example, [we saw a quality-of-life analysis and additional analyses] from the phase 3 CheckMate 8HW trial [NCT04008030]. This is not the first time [this study has been] presented—these were follow-up analyses.

Rocío García-Carbonero, MD

This study was conducted in advanced microsatellite instability–high [MSI-H]/mismatch repair–deficient advanced CRC, and this is the first randomized study that assesses, in this context, single-agent immune checkpoint inhibition with nivolumab [Opdivo], or dual inhibition with nivolumab and ipilimumab [Yervoy], vs the standard of care, which is chemotherapy with or without biologics. These [regimens] were tested in first, second, and third line, and with a dual end point.

[We saw that] giving early immune checkpoint inhibition to these patients has a benefit beyond first progression, and that’s very relevant. They compared, for the first time, nivolumab plus ipilimumab vs nivolumab, and there’s a significant improvement in PFS in that regard, with a slight increase in toxicity—but not as striking as has been seen in other tumors or maybe with other regimens, because the dose of ipilimumab that is used is not very high. It’s fairly tolerable, and the magnitude of benefit [with the addition of ipilimumab] is very [clinically] relevant.

Elez: There were 3 mini oral abstracts that shared one particular feature—and I stressed this in the discussion. All 3 were investigator-initiated trials developed by physicians and aimed at addressing [unmet medical needs] in the field of CRC.

[There were] two abstracts focused on [locally advanced rectal cancer], and the bottom-line message was that we still need biomarkers to understand which patients are candidates for total neoadjuvant therapy [in whom we] might be able to avoid surgery for the primary tumor. When identifying patients who are candidates for organ preservation, it is very important to define biomarkers. For example, we had data that could help us identify potential candidates with microsatellite stable [MSS] tumors who could still receive [immunotherapy] in the [neoadjuvant] setting.

Elena Elez, MD, PhD

[Another] abstract [looked at the phase 2 ShorTrip trial (NCT05253846) examining] the combination of short-course radiotherapy with FOLFOXIRI. We know the individual advantages of both approaches, but until now, there had been no trial combining them. The results [showed] that although pathologic complete response was achieved in a high proportion of patients, we observed a higher incidence of neutropenia and GI toxicity, which we have to consider when thinking about how to further develop this combination.

The third abstract was a very interesting clinical trial—it was the only one that attempted to answer the question of whether liquid biopsy–guided selection for panitumumab combined with [chemotherapy] could increase responses, which was the primary objective, and improve outcomes such as the rate of R0 resection. The study was [negative for the primary end point], but [plasma samples] were collected and will be analyzed, so we expect [sequential data] over the course of treatment, which could still be very informative.

BTC

Wainberg: In cholangiocarcinoma, we saw some evidence of activity of a PARP inhibitor in this group of patients with homologous recombination repair deficiencies, such as ATM mutations and others. We’re waiting for the next few studies, which are combining PARP inhibitors with different agents. We also have to consider how to identify these patients in advance, which is a critical issue.

Zev A. Wainberg, MD

In that context, we also saw real-world evidence for ivosidenib [Tibsovo] in the IDH1-mutated patient population, which reaffirms its role as a standard of care in the second-line setting for IDH1-mutated cholangiocarcinoma.

We have to think about drug development in cholangiocarcinoma a little differently. We shouldn’t use response rate as our threshold of activity in this disease, because a lot of drugs don’t have high response rates in this context. They may have stable disease control rates, and that may require us to reassess our [clinical trial] end points. It may also require us to consider short, randomized studies as opposed to single-arm trials moving forward.

HCC

Lai: [Data from] the TALENTACEstudy[NCT047126430] were presented by the Chinese group provided insight into how we could potentially integrate TACE with atezolizumab (Tecentriq) and bevacizumab (Avastin)—either separately or in combination—to reduce [risk of] local recurrence. It sheds light on how we might optimize treatment in the earlier phases of unresectable hepatocellularcarcinoma [HCC].

Connie Lai, MD

I believe this could inspire further investigation into how we can better tailor treatment approaches for patients withintermediate- to high-burden unresectable HCC, particularly in the systemic treatment-naïve setting. It was a valuable contribution to the discussion on treatment optimization in liver cancer.

Masatoshi Kudo, MD

Kudo: The late-breaking abstract on the combination of atezolizumab plus TACE showed better progression-free survival and a positive trend in overall survival [OS]. It is consistent with what has already been presented and published from the [phase 3] EMERALD-1 trial [NCT03778957)] and the REPLACE-012 [NCT04777851] trials.

Of course, the OS data are not yet mature, but I expect that this will become a treatment option in the intermediate-stage setting. The recent trend is to combine IO-based systemic therapy with locoregional therapy, and I expect this will become the new standard of care.

GEC

Shitara: The CLDN18.2– and 4-1BB–targeted agent [givastomig] already showed single-agent activity, which was recently published in Clinical Cancer Research. It showed quite a nice response rate and durable duration of treatment and durable response, and very importantly, a very nice safety profile.

Kohei Shitara, MD

To do indirect comparisons in different trials is very tricky, but it looks better in terms of GI toxicity and its tolerability compared with currently available drug formulations. 4-1BB is more tumor specific or expressed in more tumor-specific lymphocytes. [By targeting both], it may activate more tumor-specific lymphocytes without activation of lymphocytes that react to normal tissue. This is just my personal speculation, but it may be good to see such a better safety profile.

The study group is already considering a future study, and we are looking forward to further results.

Gangam-Panday: I really enjoyed the sessions on esophageal adenocarcinoma and squamous cell carcinoma, where they discussed what the current therapy is, how they look at the watch-and-wait approach, and how they evaluate all possible therapies—the chemotherapy vs chemoradiotherapy discussion. I think we can still investigate a lot, but by putting it all on a treatment pathway, we know what the options are, and we should really discuss that within our groups and with the patient to give the best possible treatment that we have right now.

There are also a lot of new therapies emerging that were discussed, like immunotherapy, chemotherapy combined with immunotherapy, or chemoradiotherapy combined with immunotherapy. Those discussions will be the future, and we should try to optimize the treatment strategies for the patients so we have the best outcomes.

Wainberg: In gastric cancer, we saw two mini oral presentations. One was a quality-of-life analysis from the phase 3 RATIONALE-305 study [NCT03777657], which—like most quality-of-life analyses—reaffirmed that patients who did better clinically also had symptomatic improvement in their disease.

Finally, we saw a retrospective review of hereditary diffuse gastric cancer [HDGC], which challenged the notion that we should operate on every patient with a diagnosis of HDGC. Sometimes, advanced endoscopic techniques can be considered in place of surgery.