166 - FAPI-Guided Radiotherapy + Cadonilimab with Systemic Therapy vs. Systemic Therapy Alone in Second-Line Treatment of Colorectal Peritoneal Metastasis (TORCH-PM01)
Presenter(s)
J. Wan1, Z. Zhang1, W. Dai2, R. Wang2, Z. Zhang3, and G. Cai2; 1Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China, 2Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China, Shanghai, Shanghai, China, 3Department of Radiation Oncology, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University; Shanghai Clinical Research Center for Radiation Oncology; Shanghai Key Laboratory of Radiation Oncology, Shanghai, China
Purpose/Objective(s): This study aims to evaluate the efficacy and safety of FAPI PET/CT-guided radiotherapy combined with second-line systemic treatment and cadonilimab compared to second-line systemic treatment alone in patients with peritoneal metastasis from colorectal cancer.
Materials/Methods: In this prospective randomized controlled trial, we enrolled patients with peritoneal metastasis from colorectal cancer who progressed after first-line systemic therapy. Patients were randomly assigned to the control group, receiving second-line standard systemic treatment (n=20), or the study group, which received hyopfractionated radiotherapy (20-25 Gy in 5 fractions) combined with second-line systemic treatment and cadonilimab (n=20). The primary endpoint was overall response rate (ORR). Surgical resectability was evaluated at multidisciplinary team (MDT) meetings every two months. A total of 40 patients were enrolled, with 19 evaluable patients in each group following loss to follow-up.
Results: The ORR was significantly higher in the study group at 63.2% (12/19) compared to 15.8% (3/19) in the control group (P=0.003). Ultimately, 12(63.2%) patients in the study group and 4(21.1%) patients in the control group underwent Cytoreductive Surgery plus Hyperthermic Intraperitoneal Chemotherapy (CRS+HIPEC) (P=0.007). Postoperative pathology revealed that pathological complete response (pCR) was achieved in 3 patients from the study group, whereas no patients in the control group attained pCR. Adverse events (AEs) of grade 3-4 in the study group included neutropenia (26.3%, 5/19), nausea (15.8%, 3/19), vomiting (15.8%, 3/19), and diarrhea (15.8%, 3/19). In the control group, the most common grade 3-4 AE was neutropenia (21.1%, 4/19) and vomiting (10.5%, 2/19). Immune-related AEs of grades 1-2 in the study group included skin reactions (15.8%, 3/19), hypothyroidism (5.3%, 1/19), hepatitis (5.3%, 1/19), and myocarditis (15.8%, 3/19). One case of grade 3-4 skin reaction (5.3%) was observed in the study group.
Conclusion: FAPI PET/CT-guided radiotherapy combined with second-line systemic treatment and cadonilimab significantly improves ORR and CRS in patients with peritoneal metastasis from colorectal cancer compared to standard second-line treatment alone, with manageable toxicity profiles. These findings support a promising therapeutic strategy for this challenging patient population. The study is registered with ClinicalTrials.gov, NCT07079462.