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Durvalumab plus pazopanib combination in patients with advanced soft tissue sarcomas: a phase II trial

Authors
 Hee Jin Cho  ;  Kum-Hee Yun  ;  Su-Jin Shin  ;  Young Han Lee  ;  Seung Hyun Kim  ;  Wooyeol Baek  ;  Yoon Dae Han  ;  Sang Kyum Kim  ;  Hyang Joo Ryu  ;  Joohee Lee  ;  Iksung Cho  ;  Heounjeong Go  ;  Jiwon Ko  ;  Inkyung Jung  ;  Min Kyung Jeon  ;  Sun Young Rha  ;  Hyo Song Kim 
Citation
 NATURE COMMUNICATIONS, Vol.15(1) : 685, 2024-01 
Journal Title
NATURE COMMUNICATIONS
Issue Date
2024-01
MeSH
Antibodies, Monoclonal* ; Humans ; Indazoles* ; Neoplasm Recurrence, Local ; Pyrimidines* ; Sarcoma* ; Soft Tissue Neoplasms* ; Sulfonamides*
Abstract
We aimed to determine the activity of the anti-VEGF receptor tyrosine-kinase inhibitor, pazopanib, combined with the anti-PD-L1 inhibitor, durvalumab, in metastatic and/or recurrent soft tissue sarcoma (STS). In this single-arm phase 2 trial (NCT03798106), treatment consisted of pazopanib 800 mg orally once a day and durvalumab 1500 mg once every 3 weeks. Primary outcome was overall response rate (ORR) and secondary outcomes included progression-free survival (PFS), overall survival, disease control rate, immune-related response criteria, and safety. The ORR was 30.4% and the trial met the pre-specified endpoint. The median PFS was 7.7 months (95% confidence interval: 5.7–10.4). The common treatment-related adverse events of grades 3–4 included neutropenia (9 [19.1%]), elevated aspartate aminotransferase (7 [14.9%]), alanine aminotransferase (5 [10.6%]), and thrombocytopenia (4 [8.5%]). In a prespecified transcriptomic analysis, the B lineage signature was a significant key determinant of overall response (P = 0.014). In situ analysis also showed that tumours with high CD20 + B cell infiltration and vessel density had a longer PFS (P = 6.5 × 10−4) than those with low B cell infiltration and vessel density, as well as better response (50% vs 12%, P = 0.019). CD20 + B cell infiltration was identified as the only independent predictor of PFS via multivariate analysis. Durvalumab combined with pazopanib demonstrated promising efficacy in an unselected STS cohort, with a manageable toxicity profile.
Files in This Item:
T202400853.pdf Download
DOI
10.1038/s41467-024-44875-2
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Biomedical Systems Informatics (의생명시스템정보학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Orthopedic Surgery (정형외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Plastic and Reconstructive Surgery (성형외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Radiology (영상의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Sang Kyum(김상겸) ORCID logo https://orcid.org/0000-0003-0768-9923
Kim, Seung Hyun(김승현) ORCID logo https://orcid.org/0000-0002-3878-1944
Kim, Hyo Song(김효송) ORCID logo https://orcid.org/0000-0002-0625-9828
Rha, Sun Young(라선영) ORCID logo https://orcid.org/0000-0002-2512-4531
Ryu, Hyang-Joo(류향주)
Baek, Wooyeol(백우열) ORCID logo https://orcid.org/0000-0002-6638-4110
Shin, Su Jin(신수진) ORCID logo https://orcid.org/0000-0001-9114-8438
Lee, Young Han(이영한) ORCID logo https://orcid.org/0000-0002-5602-391X
Lee, Joohee(이주희) ORCID logo https://orcid.org/0000-0002-7721-8935
Jeon, Min Kyung(전민경)
Jung, Inkyung(정인경) ORCID logo https://orcid.org/0000-0003-3780-3213
Cho, Ik Sung(조익성)
Han, Yoon Dae(한윤대) ORCID logo https://orcid.org/0000-0002-2136-3578
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/198066
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