Top 10 GI Oncology Studies at ESMO 2025

Based on the context provided, here are the top 10 gastrointestinal (GI) oncology studies that could be highlighted at ESMO 2025 based on their significant findings, clinical implications, and advancements in treatment strategies:

---

### **1. CheckMate-8HW (mCRC, 1L, MSI-H/dMMR)**

• **Study Design:** Comparison of nivolumab + ipilimumab versus nivolumab alone in first-line microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (mCRC).
• **Key Findings:**
• Significantly better progression-free survival (PFS) with dual-checkpoint blockade (HR ≈ 0.69).
• Higher overall response rate (ORR) compared to nivolumab alone.
• **Clinical Impact:** Confirms the advantage of dual immunotherapy in MSI-H/dMMR mCRC upfront, setting a new standard for first-line treatment in this subgroup.

---

### **2. STELLAR-303 (mCRC, previously treated, non-MSI-H)**

• **Study Design:** Zanzalintinib (VEGFR/MET/AXL TKI) + atezolizumab versus regorafenib in previously treated non-MSI-H mCRC.
• **Key Findings:**
• Improved overall survival (OS) compared to regorafenib standard-of-care.
• Demonstrates activity of VEGFR/MET/AXL-targeted therapy combined with PD-L1 blockade in proficient mismatch repair (pMMR) mCRC.
• **Clinical Impact:** Signals potential for targeted therapy and immunotherapy combinations in later-line non-MSI-H mCRC treatment.

---

### **3. MATTERHORN (Resectable Gastric/GEJ Adenocarcinoma)**

• **Study Design:** Peri-operative durvalumab + FLOT chemotherapy versus FLOT alone.
• **Key Findings:**
• Improved overall survival (OS) with the addition of durvalumab.
• **Clinical Impact:** Supports integrating PD-L1 blockade into peri-operative FLOT for fit patients with resectable gastric and gastroesophageal junction (GEJ) adenocarcinoma.

---

### **4. CASANDRA (Resectable/Borderline-Resectable Pancreatic Cancer)**

• **Study Design:** Short-course PAXG regimen versus long-course modified FOLFIRINOX (mFOLFIRINOX).
• **Key Findings:**
• Event-free survival (EFS) improved with short-course nab-paclitaxel–based PAXG regimen.
• **Clinical Impact:** Demonstrates that a shorter and more tolerable regimen can rival and outperform long-course mFOLFIRINOX for peri-operative control in pancreatic cancer.

---

### **5. GFH375X1201 (KRAS G12D-Mutant Pancreatic Cancer, Previously Treated)**

• **Study Design:** KRAS-G12D inhibitor monotherapy.
• **Key Findings:**
• Objective response rate (ORR) ≈ 41%.
• Median progression-free survival (PFS) ≈ 5.5 months.
• **Clinical Impact:** Represents one of the strongest signals for a single-agent KRAS-targeted therapy in KRAS-G12D-mutant pancreatic ductal adenocarcinoma (PDAC).

---

### **6. KC-WISE (HER2+ Gastric/GEJ Cancer, Post-Trastuzumab)**

• **Study Design:** Abemintamab (bispecific anti-HER2) + chemotherapy versus chemotherapy alone.
• **Key Findings:**
• Improved progression-free survival (PFS) and overall survival (OS).
• **Clinical Impact:** Suggests durable benefit for next-generation HER2 bispecifics in HER2+ gastric/GEJ cancer after trastuzumab.

---

### **7. ZSAB-neoGOLP (Resectable High-Risk Intrahepatic Cholangiocarcinoma)**

• **Study Design:** Neoadjuvant toripalimab (PD-1 inhibitor) + lenvatinib (VEGFR inhibitor) + GEMOX (gemcitabine + oxaliplatin) versus upfront surgery.
• **Key Findings:**
• Median event-free survival (EFS) of 18.0 months versus 8.7 months with upfront surgery.
• **Clinical Impact:** Strengthens the case for integrating immunotherapy, targeted therapy, and chemotherapy in neoadjuvant settings for high-risk intrahepatic cholangiocarcinoma (iCCA).

---

### **8. FORTITUDE-101 (FGFR2b-Overexpressing Gastric/GEJ Cancer)**

• **Study Design:** Bemarituzumab (anti-FGFR2b) + mFOLFOX6 chemotherapy in biomarker-selected patients.
• **Key Findings:**
• Statistically significant overall survival (OS) benefit at primary analysis.
• **Clinical Impact:** Reinforces FGFR2b as a validated therapeutic target in gastric/GEJ cancer, particularly in biomarker-selected patients.

---

### **9. ABC-HCC (Intermediate-Stage, Unresectable Hepatocellular Carcinoma [HCC])**

• **Study Design:** Atezolizumab (PD-L1 inhibitor) + bevacizumab (VEGF inhibitor) versus transarterial chemoembolization (TACE).
• **Key Findings:**
• Improved time-to-treatment failure (~14.6 months vs 9.5 months).
• **Clinical Impact:** Positions immune-oncology (IO)-VEGF combinations as a potential alternative to TACE in intermediate-stage HCC (BCLC-B patients).

---

### **10. CITRIC (Chemorefractory RAS/BRAF Wild-Type mCRC)**

• **Study Design:** Circulating tumor DNA (ctDNA)-guided anti-EGFR "re-challenge" strategy versus standard options.
• **Key Findings:**
• Improved progression-free survival (PFS) and overall survival (OS) in RAS/BRAF wild-type mCRC.
• **Clinical Impact:** Validates liquid-biopsy–guided re-challenge with anti-EGFR therapy as an effective strategy in chemorefractory mCRC.

---

### Summary:

These landmark studies represent significant advancements in GI oncology, spanning colorectal, gastric, pancreatic, cholangiocarcinoma, and hepatocellular cancers. They highlight the importance of personalized medicine, targeted therapies, novel combinations of immunotherapy, and the role of biomarkers in guiding treatment decisions. These findings are poised to reshape treatment paradigms and improve outcomes for patients across various GI malignancies.

Let me know if you'd like me to prepare a one-page handout or slide summarizing this update for your meeting!