Abstract: Objective: To evaluate the efficacy and safety of a combination treatment modality of stereotactic radiotherapy (SBRT) in combination with liposomal irinotecan, karelizumab, and antiangiogenic pharmacotherapy (CAP) in patients with advanced soft tissue sarcoma.
Methods: Retrospective analysis of patients with soft tissue sarcoma enrolled in the CAP clinical study between November 2020 and February 2023.The CAP trial was a multicenter, open-label, single-arm, phase II clinical study enrolling 60 patients with advanced solid tumors that had progressed after standard treatment, including 11 patients with soft tissue sarcoma, who were given 15-24 Gy/3f of massively fractionated radiotherapy sequential Intravenous chemotherapy with liposomal irinotecan (80 mg/m2) in combination with maintenance therapy with karelizumab (200 mg, q3w) and anti-angiogenic agents (apatinib 250 mg, qd, preferred) until disease progression or intolerable toxicity. This study used a retrospective analysis to statistically compare the efficacy and safety of advanced soft tissue sarcoma (STS) and non-soft tissue sarcoma cases enrolled in the CAP trial.
Results: A total of 11 patients in the STS group were included in this study, with an ORR of 27.3% and a DCR of 72.7% in the STS group. The median PFS was 8 months and OS was not yet reached. Common grade 3-4 adverse reactions included lymphopenia (31.7%), anemia (10%), and leukopenia (10%), and no treatment-related deaths were seen.Cox regression analysis showed that elevated lactate dehydrogenase (LDH), NLR ≥4, and maximal lesion >5 cm were significantly associated with poorer survival prognosis (P<0.05). The median PFS in the non-STS group was 4 months, and the 1-year OS rate was 69.39%.
Conclusion: SBRT combined with liposomal irinotecan, karelizumab and anti-angiogenic therapy showed good anti-tumor activity and manageable toxicity in advanced STS patients who failed multiple lines of therapy or had no standard treatment, especially with high response rate for subtypes such as undifferentiated sarcoma, which warrants further large-scale randomized controlled studies.