ESMO 2025 GI Cancer Data Highlight Emerging Precision Strategies and Treatment Avenues for Rare Cancers

The 2025 ESMO Congress saw the presentation of several potentially practice-changing studies across gastrointestinal (GI) disease subsets, from novel data in pancreatic and biliary tract cancers to insights that may inform the future management of rare GI cancers.

In the wake of the meeting, OncLive® spoke with the following GI oncology experts about the updates they were most excited to see at this year’s Congress:

• James J. Harding, MD, an associate attending physician at Memorial Sloan Kettering Cancer Center in New York, New York
• Jaume Capdevila, MD, a medical oncologist in the Gastrointestinal and Endocrine Cancer Unit in the Medical Oncology Department at Vall d’Hebron Hospital and the Teknon Cancer Institute at the Institute of Oncology Hospital Quirónsalud Barcelona in Spain

Read on for exclusive insights on developments across this treatment paradigm!

Moving the Needle in HCC, Pancreatic, and Biliary Tract Cancers

Harding: I focus on hepatopancreaticobiliary cancers. There was lot of note at ESMO 2025. We've seen in pancreas cancer the continued role of RAS targeting. In hepatocellular carcinoma, we saw the utilization of immunotherapies at earlier stages of disease, which is showing an interesting signal. Some studies have been pushing us in that direction for biliary tract cancers. We've also seen interesting concepts related to the perioperative implementation of chemoimmunotherapies and targeted therapies, such as those targeting FGFR2 fusions. [Additionally, we’ve seen data with] many antibody-drug conjugates (ADCs). The future is looking brighter for these cancer types, and it's going to be great to see how these initial studies will play out globally in the upcoming years.

Telisotuzumab Adizutecan in PDAC: Notable Highlights1

1. In this phase 1 basket trial (NCT06084481), telisotuzumab adizutecan (Temab-A; ABBV-400) demonstrated antitumor activity in the overall cohort of 42 previously treated patients with pancreatic ductal adenocarcinoma (PDAC; n = 40), who achieved a confirmed objective response rate (cORR) of 23.8% and a median overall survival (OS) of 7.9 months.
2. The effectiveness of Temab-A varied based on patients’ prior first-line therapy, with patients previously treated with gemcitabine plus nab-paclitaxel achieving a higher cORR of 40.0% and a median OS of 11.6 months compared with a 15.4% cORR and a 7.1-month median OS for those previously treated with FOLFIRINOX (leucovorin, 5-fluorouracil [5-FU], irinotecan, and oxaliplatin).
3. Temab-A was associated with a manageable safety profile in PDAC, consistent with its activity as a c-Met–targeting ADC. The most common treatment-emergent adverse effects (TEAEs) wereGI and hematologic toxicities, which were often managed by dose modifications.

Read more about this phase 1 trial through OncLive’s coverage here!

MATTERHORN Trial: Final OS Analysis Insights2

1. In this phase 3 trial (NCT04592913), durvalumab plus FLOT (5-FU, leucovorin, oxaliplatin, and docetaxel; n = 474) yielded a statistically significant and clinically meaningful improvement in OS compared with placebo plus FLOT (n = 474) in the intent-to-treat population of patients with resectable gastric/GEJ adenocarcinoma (HR, 0.78; 95% CI, 0.63–0.96; P = .021).
2. Any degree of pathological response was associated with improved event-free survival (EFS) with durvalumab plus FLOT vs placebo plus FLOT. The 24-month EFS rate among patients who achieved any pathological response was 78.3% in the durvalumab/FLOT arm (n = 346) compared with 68.0% in the placebo/FLOT arm (n = 313).
3. The rate of patients who achieved ypN-negative disease was higher among evaluable patients receiving durvalumab plus FLOT (n = 411), at 58.2% compared with 44.8% among those receiving placebo plus FLOT (n=400).

Read on for OncLive’s exclusive coverage of MATTERHORN!

Spotlighting Research in Endocrine and Neuroendocrine Tumors

Capdevila: We should [give] a big thanks to ESMO, because [this meeting showed data with] independent drugs for endocrine and neuroendocrine cancers. Compared with [the ASCO Annual Meeting], for instance, [where endocrine and neuroendocrine cancer research is] included in [studies that also include] other kind of cancers, [at ESMO 2025] we had a huge representation of endocrine and neuroendocrine cancers. This means that ESMO is the best platform in the world today to present new data on neuroendocrine tumors [NETs]. [Results from] phase 3 studies coming from China [were presented, as well as] new data on alpha inhibitors. We have new compounds—HIF2α inhibitors—that have shown efficacy in pheochromocytomas and paragangliomas, for instance. Those are types of NETs. Also, [we saw a presentation of] data on belzutifan [Welireg] in pancreatic NETs. We should thank ESMO, and maybe other societies [should follow this example] because for rare cancers, it's extremely important to show that we have a lot of research and practice-changing studies.

ALPHAMEDIX-02 trial: Takeaway Points3

1. In this phase 2 trial (NCT05153772), radioligand therapy–naive patients with advanced gastroenteropancreatic NETs (GEP-NETs; n = 35), 212Pb-DOTAMTATE (AlphaMedix) demonstrated high efficacy, producing an ORR of 60.0% (95% CI, 42.1%-76.1%) and a disease control rate of 94.3% (95% CI, 80.8%-99.3%).
2. Longer-term follow-up showed durable clinical benefit in this population, with a 36-month progression-free survival (PFS) rate of 72.3% (95% CI, 53.3%-84.5%) and a 36-month OS rate of 88.2% (95% CI, 71.5%-95.4%).
3. The safety profile of 212Pb-DOTAMTATE was acceptable, as 85.7% of patients completed all 4 doses of the therapy, and no cases of myelodysplastic syndromes or acute myeloid leukemia were reported.

Check out more from ALPHAMEDIX-02 in this OncLive article!

COMPETE Trial: Key Findings4

1. The phase 3 COMPETE trial (NCT03049189) met its primary end point, demonstrating that the median PFS assessed centrally by blinded independent central review was significantly longer in patients with GEP-NETs who received177-Lu-edotretide (ITM-11; n = 207), at 23.9 months (95% CI, 18.7-30.0) compared with 14.1 months (95% CI, 9.2-20.9) among those who received everolimus (Afinitor; n = 102; HR, 0.67; 95% CI, 0.48-0.95; P = .022).
2. The ORR, a key secondary end point, was significantly higher in the 177-Lu-edotretide arm, at 21.9% compared with 4.2% with everolimus (P < .0001).
3. 177-Lu-edotretide had a favorable safety profile compared with everolimus. Rates of related TEAEs leading to premature study discontinuation were significantly lower in the 177-Lu-edotretide arm (1.8%) vs the everolimus arm (15.2%).

Read more about COMPETE through OncLive’s coverage of the data!

References

1. Harding JJ, Strickler J, Henry J, et al. Phase 1 basket study of telisotuzumab adizutecan (ABBV-400; Temab-A), a c-Met protein–targeting antibody-drug conjugate: results from patients with pancreatic ductal adenocarcinoma. Presented at the European Society for Medical Oncology (ESMO) Congress 2025; October 17-21, 2025; Berlin, Germany. Abstract 2214MO.
2. Tabernero, J. 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 17–20, 2025; Berlin, Germany. Abstract LBA81.
3. Strosberg JR, Naqvi S, Cohn A, et al. Efficacy and safety of targeted alpha therapy 212Pb-DOTAMTATE in patients with unresectable or metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs) previously treated with peptide receptor radionuclide therapy (PRRT): results of a phase II study. Presented at: 2025 ESMO Congress; October 17-21, 2025; Berlin, Germany. Abstract 1032O.
4. Capdevilla J, Amthauer H, Ansquer C, et al. Efficacy, safety and subgroup analysis of 177Lu-edotreotide vs everolimus in patients with grade 1 or grade 2 GEP-NETs: Phase 3 COMPETE trial. Presented at: 2025 ESMO Congress; October 17-20, 2025; Berlin, Germany. Abstract 1706O