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Luo H, Zhai ZL, Xu J, Li X, Chen YW, Bai XL. Durable disease control with multimodal treatment including fulzerasib, cetuximab and radiotherapy in locally advanced pancreatic cancer: A case report. World J Gastrointest Oncol 2026; 18(12): 125300 [DOI: 10.4251/wjgo.125300]
World J Gastrointest Oncol. Dec 15, 2026; 18(12): 125300 Published online Dec 15, 2026. doi: 10.4251/wjgo.125300
Durable disease control with multimodal treatment including fulzerasib, cetuximab and radiotherapy in locally advanced pancreatic cancer: A case report
Huan Luo, Zheng-Long Zhai, Jian Xu, Xiang Li, Yi-Wen Chen, Xue-Li Bai, Department of Hepatobiliary and Pancreatic Surgery, Zhejiang University School of Medicine, Hangzhou 310000, Zhejiang Province, China
Author contributions: Luo H and Chen YW had full access to all data in the study and take responsibility for the integrity and accuracy of the data analysis, they were involved in the acquisition, analysis, and interpretation of patient data, as well as the drafting of the manuscript; Zhai ZL, Xu J, and Li X contributed to the acquisition of clinical and pathological data, and critically revised the manuscript for important intellectual content; Chen YW and Bai XL developed the concept and design of this combination treatment, coordinated the overall treatment process, and supervised the data analysis; and all authors read, critically revised, and approved the final manuscript.
AI contribution statement: No AI tool was used to generate research data, interpret results, language polishing, or formulate conclusions.
Supported by Ling Yan Research and Development Program of Department of Zhejiang Province Science and Technology, No. 2026C02A1105 and No. 2024C03167.
Informed consent statement: The patient has signed the informed consent form
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
CARE Checklist (2016) statement: The authors have read the CARE Checklist (2016), and the manuscript was prepared and revised according to the CARE Checklist (2016).
Corresponding author: Yi-Wen Chen, MD, Associate Chief Physician, Department of Hepatobiliary and Pancreatic Surgery, Zhejiang University School of Medicine, No. 79 Qingchun Road, Hangzhou 310000, Zhejiang Province, China. cherry0705@zju.edu.cn
Received: July 6, 2026 Revised: August 1, 2026 Accepted: September 15, 2026 Published online: December 15, 2026 Processing time: 127 Days and 1.3 Hours
Abstract
BACKGROUND
Pancreatic ductal adenocarcinoma carries a dismal prognosis, with limited therapeutic options for patients with advanced disease. Although KRAS mutations are nearly ubiquitous in pancreatic ductal adenocarcinoma, the rare KRAS G12C subtype (1%-2% of cases) has recently become therapeutically actionable. Combining KRAS G12C inhibitors with anti-epidermal growth factor receptor antibodies may enhance efficacy by blocking compensatory epidermal growth factor receptor pathway reactivation, yet this strategy has not been reported in pancreatic cancer.
CASE SUMMARY
An 81-year-old man was diagnosed with locally advanced pancreatic cancer (cT4N×M0) harboring a KRAS G12C mutation (variant allele frequency 20.54%), concurrent CDKN2A and TP53 mutations, low tumor mutational burden, and microsatellite stability. Given his advanced age and comorbidities, conventional chemotherapy was deemed unsuitable. The patient received a multimodal therapeutic regimen consisting of systemic targeted therapy with fulzerasib and weekly cetuximab, combined with intensity-modulated carbon-ion radiotherapy. Treatment was generally well tolerated, treatment-related toxicities and infection-associated events were manageable, and no grade 4 or higher treatment-related adverse events occurred. Carbohydrate antigen 19-9 declined from 45.4 U/mL to within the normal range during treatment. Imaging assessments consistently demonstrated stable disease, and positron emission tomography/computed tomography at approximately 14 months confirmed minimal residual tumor activity. As of the last follow-up, progression-free survival exceeded 19 months with ongoing disease control and substantially improved quality of life.
CONCLUSION
This multimodal strategy demonstrated durable disease control and manageable safety, supporting further study in KRAS G12C-mutant pancreatic cancer.
Core Tip: This report presents the first known clinical application of a multimodal regimen combining the KRAS G12C inhibitor fulzerasib, the epidermal growth factor receptor antibody cetuximab, and localized carbon-ion radiotherapy in locally advanced pancreatic cancer harboring a KRAS G12C mutation. The treatment yielded durable disease control, extending progression-free survival beyond 19 months with a manageable safety profile in an 81-year-old patient unfit for conventional chemotherapy. This novel precision approach highlights the potential of combining dual-pathway targeted therapy with heavy-ion radiotherapy for KRAS-mutated locally advanced pancreatic cancer.
