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This study aimed to evaluate the effectiveness and safety of sintilimab, a programmed cell death protein-1 (PD-1) blockade, combined with sorafenib and transhepatic arterial chemotherapy and embolization in this patient population, compared with sintilimab monotherapy and sintilimab-sorafenib duotherapy. This was a 22\u00a0months single center retrospective cohort study in China. 80 patients with unresectable hepatocellular carcinoma were included, with diagnosis confirmed by either histologic, cytologic or diagnostic imaging analysis. The patients were divided into three groups based on therapeutic regimen: sintilimab monotherapy (sintilimab group, n\u2009=\u200922), sintilimab-sorafenib duotherapy (duplex group, n\u2009=\u200923), sintilimab-sorafenib and transcatheter arterial chemoembolization combined therapy (triple group, n\u2009=\u200935). The principal evaluation criteria were overall survival and progression free survival in the population, assessed according to response evaluation criteria in solid tumors, version 1.1 (RECIST 1.1). Secondary evaluation criteria were safety, objective response rate and disease control rate. From March 1st, 2019 to December 31, 2020, 80 patients with unresectable hepatocellular carcinoma were included and divided into three treatment groups (22 received sintilimab monotherapy, 23 received sintilimab-sorafenib duotherapy, and 35 received sintilimab-sorafenib combined with transcatheter arterial chemoembolization). The median overall survival of all patients was 11.0\u00a0months (95% CI 7.7\u201314.3). Median overall survival was 13.0\u00a0months (95% CI NE\u2013NE), 9.0\u00a0months(95% CI 6.3\u201311.7)and 3.0\u00a0months (95% CI 1.9\u20134.1, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001) in the triple therapy, duplex and sintilimab groups respectively, while the corresponding median progression-free survival were 5.0\u00a0months (95% CI 2.9\u20137.1, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001), 4.0\u00a0months (95% CI 2.8\u20135.2) and 2.0\u00a0months (95% CI 1.7\u20132.3). Disease control and clinical benefits rates were higher in the triple therapy group (80%, 95% CI 63.1\u201391.6, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001; 54.3%, 95% CI 36.6\u201371.2, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01) compared to the sintilimab group. Median duration of disease control was 4.0\u00a0months (95% CI NE\u2013NE, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01) in the triple therapy group, longer than that of the duplex group (2.0\u00a0months, 95% CI 0.9\u20133.1) and sintilimab group (2.0\u00a0months, 95% CI 0.8\u20133.2). Grade 3 or 4 treatment-related adverse events occurred in 26.3% of 80 patients with hypertension was the most common event observed (38, 47.5%), however, other severe toxic effects were infrequent. Sintilimab combined with sorafenib and transcatheter arterial chemoembolization might have more beneficial effects on overall and progression-free survival and on the duration of disease control outcomes than both sintilimab monotherapy and sintilimab-sorafenib duotherapy in patients with unresectable hepatocellular carcinoma. This triple therapy model might represent an innovative and effective option for inoperable liver cancer.\n<\/jats:p>","DOI":"10.1038\/s41598-021-98937-2","type":"journal-article","created":{"date-parts":[[2021,10,5]],"date-time":"2021-10-05T13:52:53Z","timestamp":1633441973000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Therapeutic effectiveness and safety of sintilimab-dominated triple therapy in unresectable hepatocellular carcinoma"],"prefix":"10.1038","volume":"11","author":[{"given":"Lei","family":"Dai","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xingchen","family":"Cai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph","family":"Mugaanyi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yelei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuqi","family":"Mao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Changjiang","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caide","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,10,5]]},"reference":[{"issue":"6","key":"98937_CR1","doi-asserted-by":"publisher","first-page":"394","DOI":"10.3322\/caac.21492","volume":"68","author":"F Bray","year":"2018","unstructured":"Bray, F. et al. 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