PMID- 36582535 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20230103 IS - 1663-9812 (Print) IS - 1663-9812 (Electronic) IS - 1663-9812 (Linking) VI - 13 DP - 2022 TI - Efficacy and safety of sintilimab plus doxorubicin in advanced soft tissue sarcoma: A single-arm, phase II trial. PG - 987569 LID - 10.3389/fphar.2022.987569 [doi] LID - 987569 AB - Background: Chemoimmunotherapy is safe and efficacious in treating many types of malignant tumors. However, clinical data demonstrating the effect of this combination treatment in patients with metastatic soft tissue sarcoma (STS) are currently limited. This study evaluated the safety and efficacy of a programmed cell death protein 1 (PD-1) inhibitor plus doxorubicin in patients with advanced STS who failed previous systemic therapy. Methods: This was a single-center, single-arm, open-label phase II trial. Patients with unresectable or metastatic STS who had previously failed systemic therapy were enrolled. Patients received up to six cycles of doxorubicin and sintilimab (a PD-1 inhibitor), while sintilimab treatment continued for up to 2 years. Primary outcomes were objective response rate (ORR) and safety. Univariate Cox proportional hazards model was used to analyze the relationship between clinicopathological parameters and progression-free survival (PFS). Results: A total of 38 patients (20 men and 18 women) were enrolled in this study. The overall ORR was 39.5%, disease control rate was 71.1%, and the median PFS was 4.5 months [95% confidence interval (CI), 3.0-8.5 months]. The adverse events (AEs) associated with the combined treatment were mild, manageable, and well-tolerated. The most common grade 3 or higher AEs were hematologic, including leukopenia (21.1%), anemia (18.4%), and thrombocytopenia (18.4%). Patients with undifferentiated pleomorphic sarcoma (UPS) or dedifferentiated liposarcoma had a significantly longer PFS than those with other pathological subtypes [hazard ratio (HR) = 0.42, 95% CI 0.21-0.83; p = 0.013]. There was no significant difference in the median PFS between patients who had previously received anthracycline-based chemotherapy and those who had not (HR = 0.74, 95% CI 0.34-1.58, p = 0.43). Conclusion: Sintilimab plus doxorubicin is a safe and promising treatment for patients with advanced STS who have failed previous systemic therapy (including anthracycline-based chemotherapy). The efficacy of this combination therapy in UPS and dedifferentiated liposarcoma is superior to that in other sarcomas. Clinical Trial Registration: https://www.chictr.org.cn, registration number: ChiCTR1900027009. CI - Copyright (c) 2022 Tian, Dong, Zuo, Li, Zhang, Gao, Yang, Li, Zhang, Wang, Wang and Yao. FAU - Tian, Zhichao AU - Tian Z AD - Department of Bone and Soft Tissue, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, China. FAU - Dong, Shuping AU - Dong S AD - Department of Bone and Soft Tissue, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, China. FAU - Zuo, Wenli AU - Zuo W AD - Department of Hematology, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, China. FAU - Li, Po AU - Li P AD - Department of Bone and Soft Tissue, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, China. FAU - Zhang, Fan AU - Zhang F AD - Department of Bone and Soft Tissue, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, China. FAU - Gao, Shilei AU - Gao S AD - Department of Bone and Soft Tissue, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, China. FAU - Yang, Yonghao AU - Yang Y AD - Department of Immunotherapy, The Affiliated Cancer Hospital of Zhengzhou University, Henan, Zhengzhou, China. FAU - Li, Chao AU - Li C AD - Department of Bone and Soft Tissue, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, China. FAU - Zhang, Peng AU - Zhang P AD - Department of Bone and Soft Tissue, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, China. FAU - Wang, Xin AU - Wang X AD - Department of Bone and Soft Tissue, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, China. FAU - Wang, Jiaqiang AU - Wang J AD - Department of Bone and Soft Tissue, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, China. FAU - Yao, Weitao AU - Yao W AD - Department of Bone and Soft Tissue, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, China. LA - eng PT - Journal Article DEP - 20221006 PL - Switzerland TA - Front Pharmacol JT - Frontiers in pharmacology JID - 101548923 PMC - PMC9793899 OTO - NOTNLM OT - PD-1 inhibitor OT - chemoimmunotherapy OT - chemotherapy OT - dedifferentiated liposarcoma OT - undifferentiated pleomorphic sarcoma COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2022/12/31 06:00 MHDA- 2022/12/31 06:01 PMCR- 2022/10/06 CRDT- 2022/12/30 02:25 PHST- 2022/07/06 00:00 [received] PHST- 2022/09/20 00:00 [accepted] PHST- 2022/12/30 02:25 [entrez] PHST- 2022/12/31 06:00 [pubmed] PHST- 2022/12/31 06:01 [medline] PHST- 2022/10/06 00:00 [pmc-release] AID - 987569 [pii] AID - 10.3389/fphar.2022.987569 [doi] PST - epublish SO - Front Pharmacol. 2022 Oct 6;13:987569. doi: 10.3389/fphar.2022.987569. eCollection 2022.