ESMO 2026: Survival Gains and New Treatment Strategies in GI Cancers

From targeted therapies that extend survival in pancreatic cancer to immunotherapy strategies that may preserve the rectum in selected patients, new data presented at the 2026 European Society for Medical Oncology (ESMO) Congress highlighted several evolving approaches to gastrointestinal (GI) cancer treatment. Findings from 5 late-breaking presentations spanning pancreatic, colorectal, rectal, gastric, and gastroesophageal cancers offered new insights into treatment efficacy, response durability, and the potential role of biomarker-directed therapies.

Daraxonrasib Improves Survival in Previously Treated Pancreatic Cancer

Additional subgroup analyses from the phase 3 RASolute 302 study (NCT06625320) showed that daraxonrasib, a RAS(ON) multiselective inhibitor, improved overall survival (OS) compared with chemotherapy in patients with previously treated metastatic pancreatic ductal adenocarcinoma (mPDAC).¹ Median OS was 13.2 months with daraxonrasib vs 6.7 months with chemotherapy (HR, 0.40; 95% CI, 0.30-0.53).

The survival benefit was observed across RAS genotype subgroups, including regardless of identified tumor RAS mutational status. Objective response rate (ORR) and progression-free survival (PFS) generally favored daraxonrasib across subgroups, with consistent OS benefits across chemotherapy regimens and prior treatment settings, including early metastatic recurrence following perioperative therapy. These findings further characterize the activity of daraxonrasib, approved for previously treated mPDAC in late August 2026, across clinically relevant subgroups of previously treated metastatic disease.

Dostarlimab Shows Activity in Locally Advanced Rectal Cancer

Results from the registrational AZUR-1 trial (NCT05723562) demonstrated clinical complete responses (cCRs) with dostarlimab (Jemperli) monotherapy in patients with mismatch repair–deficient (dMMR)/microsatellite instability–high (MSI-H) locally advanced rectal cancer.² For this population, immune checkpoint inhibition may offer an alternative to standard multimodality treatment, which typically includes chemoradiation and surgery and can carry substantial morbidity.

Response assessments incorporated clinical examination, endoscopy, and rectal MRI. The study reported a high rate of cCR with dostarlimab alone, supporting further evaluation of nonoperative management in patients whose tumors respond completely. Continued follow-up will be important to establish response durability and determine whether patients can maintain organ preservation without compromising long-term disease control.

CheckMate 8HW Shows Survival Benefit With Dual Immunotherapy

Final OS results from the phase 3 CheckMate 8HW trial (NCT04008030) demonstrated a survival benefit with nivolumab (Opdivo) plus ipilimumab (Yervoy) in patients with MSI-H/dMMR metastatic colorectal cancer.³ In the first-line setting, the combination reduced the risk of death by 63% compared with chemotherapy (HR, 0.37; 95% CI, 0.24-0.57; P < .0001), despite 79.8% of patients assigned to chemotherapy subsequently receiving immunotherapy.

Across treatment lines, nivolumab plus ipilimumab also improved OS compared with nivolumab alone (HR, 0.61; 95% CI, 0.46-0.82; P = .0009). In the first-line comparison, 5-year OS rates were 77% with combination therapy and 66% with nivolumab monotherapy, although the first-line OS comparison between the 2 immunotherapy regimens did not meet the prespecified threshold for statistical significance. Extended follow-up showed sustained efficacy, with no new safety signals reported.

Arcotatug Tavatecan Improves Outcomes in Advanced Gastric Cancer

The phase 3 G-HOPE-001 study (NCT06238843) compared arcotatug tavatecan with physician’s choice of treatment in patients with previously treated advanced gastric or gastroesophageal junction adenocarcinoma.⁴ The antibody-drug conjugate improved PFS, with the updated analysis showing an HR of 0.45 (95% CI, 0.35-0.58). At the September 2026 interim analysis, treatment was also associated with an approximately 43% reduction in the risk of death compared with physician’s choice.

The ORR was 37.4% with arcotatug tavatecan vs 7.7% with control treatment, and median duration of response was 9.9 months with the investigational therapy. The findings indicate antitumor activity in previously treated disease, although continued follow-up will be needed to characterize the durability of benefit and longer-term safety.

Zanidatamab Regimens Improve Survival in HER2-Positive Gastroesophageal Cancer

Updated results from the phase 3 HERIZON-GEA-01 trial (NCT05152147) showed sustained OS benefits with zanidatamab (Ziihera) plus chemotherapy, with or without tislelizumab (Tevimbra), compared with trastuzumab (Herceptin) plus chemotherapy in previously untreated HER2-positive advanced or metastatic gastroesophageal adenocarcinoma.⁵ At a median follow-up of 35.3 months, median OS was 22.9 months with zanidatamab plus chemotherapy vs 19.6 months with trastuzumab plus chemotherapy (HR, 0.76; 95% CI, 0.62-0.93; P = .0088).

The triplet regimen of zanidatamab, tislelizumab, and chemotherapy was associated with a median OS of 27.0 months (HR, 0.65; 95% CI, 0.52-0.80 vs trastuzumab plus chemotherapy), with 3-year OS rates of 40% and 23%, respectively. Median PFS was 12.7 months with the triplet, 12.4 months with zanidatamab plus chemotherapy, and 8.3 months with trastuzumab plus chemotherapy. Although the triplet showed a numerical survival advantage over zanidatamab plus chemotherapy, the analysis was not powered to establish superiority between the 2 zanidatamab-containing regimens. The findings support further consideration of HER2-directed treatment strategies in this setting.

REFERENCES

1. Wainberg ZA. Daraxonrasib, a RAS(ON) multi-selective inhibitor vs chemotherapy in previously treated metastatic pancreatic adenocarcinoma (mPDAC): additional subgroup analyses from the phase 3 RASolute 302 study. Abstract LBA82. Presented at: European Society for Medical Oncology (ESMO) Congress 2026; October 23, 2026; Madrid, Spain.

2. Cercek A. Clinical complete response with dostarlimab monotherapy in dMMR/MSI-H locally advanced rectal cancer: first results from the longitudinal AZUR-1 trial. Abstract LBA87. Presented at: European Society for Medical Oncology (ESMO) Congress 2026; October 2026; Madrid, Spain.

3. Lonardi S. Final overall survival results from CheckMate 8HW in patients with microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer. Abstract LBA32. Presented at: European Society for Medical Oncology (ESMO) Congress 2026; October 2026; Madrid, Spain.

4. Shitara K. Arcotatug tavatecan vs treatment of physician’s choice in previously treated, advanced gastric or gastroesophageal junction adenocarcinoma: results from the phase 3 G-HOPE-001 study. Abstract LBA77. Presented at: European Society for Medical Oncology (ESMO) Congress 2026; October 23, 2026; Madrid, Spain.

5. Shitara K. Zanidatamab plus chemotherapy with or without tislelizumab for first-line HER2-positive advanced/metastatic gastroesophageal adenocarcinoma: second interim analysis from HERIZON-GEA-01. Abstract LBA79. Presented at: European Society for Medical Oncology (ESMO) Congress 2026; October 23, 2026; Madrid, Spain.