{"title":"durvalumab联合tremelimumab治疗不可切除肝细胞癌的抗肿瘤作用和免疫介导的不良事件","authors":"Takanori Ito, Shigeo Shimose, Joji Tani, Tetsu Tomonari, Issei Saeki, Yasuto Takeuchi, Takeshi Hatanaka, Kyo Sasaki, Satoru Kakizaki, Yuki Kanayama, Naoki Yoshioka, Takehito Naito, Mamiko Takeuchi, Tetsuya Yasunaka, Masahiro Sakata, Hideki Iwamoto, Satoshi Itano, Tomotake Shirono, Norikazu Tanabe, Takafumi Yamamoto, Atsushi Naganuma, Sohji Nishina, Motoyuki Otsuka, Taro Takami, Tetsuji Takayama, Takumi Kawaguchi, Hiroki Kawashima, Hepatology InVestigator Experts in Japan (HIVE-J) Study Group","doi":"10.1111/hepr.14151","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Aim</h3>\n \n <p>Durvalumab plus tremelimumab (Dur/Tre) is a first-line systemic treatment option for unresectable hepatocellular carcinoma (uHCC). However, the management of severe immune-mediated adverse events (imAEs) is challenging. Therefore, we investigated the relationship between severe imAEs and antitumor responses in patients with uHCC treated with Dur/Tre.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>We included 157 patients with uHCC treated with Dur/Tre in this multicenter, retrospective study and analyzed the relationship between progression-free survival (PFS)/antitumor response and severe imAEs requiring high-dose corticosteroid treatment.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>Thirty-two patients (20.4%) developed severe imAEs, including enterocolitis/diarrhea (<i>n</i> = 10), liver injury (<i>n</i> = 9), interstitial lung disease (<i>n</i> = 5), rashes (<i>n</i> = 4), cytokine-release syndrome/fever (<i>n</i> = 2), pancreatitis (<i>n</i> = 2), and others (<i>n</i> = 4) (median follow-up period, 6.8 months). Infliximab was administered in six patients with steroid-refractory enterocolitis. Although the objective response rate (ORR) and disease control rate (DCR) were significantly higher with first-line therapy than with later-line therapy (<i>p</i> = 0.026), the frequency of severe imAEs was not significantly different (<i>p</i> = 0.221). The ORR and DCR in patients with and without severe imAEs were 15.6% and 17.6% and 65.6% and 47.2%, respectively, with no significant differences. Five patients with severe imAEs, including rashes and liver injury, showed objective responses (partial response + complete response). Among patients who achieved an objective response, the PFS at 10 months was good (100% and 70.3% with and without high-dose corticosteroids, respectively).</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>Severe imAEs of Dur/Tre treatment requiring high-dose corticosteroid treatment did not affect antitumor efficacy, which differed depending on the type of imAEs. Therefore, appropriately managing imAEs is essential to guide sequential treatment.</p>\n </section>\n </div>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"55 4","pages":"577-587"},"PeriodicalIF":3.4000,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hepr.14151","citationCount":"0","resultStr":"{\"title\":\"Antitumor effects and immune-mediated adverse events of durvalumab plus tremelimumab treatment for unresectable hepatocellular carcinoma\",\"authors\":\"Takanori Ito, Shigeo Shimose, Joji Tani, Tetsu Tomonari, Issei Saeki, Yasuto Takeuchi, Takeshi Hatanaka, Kyo Sasaki, Satoru Kakizaki, Yuki Kanayama, Naoki Yoshioka, Takehito Naito, Mamiko Takeuchi, Tetsuya Yasunaka, Masahiro Sakata, Hideki Iwamoto, Satoshi Itano, Tomotake Shirono, Norikazu Tanabe, Takafumi Yamamoto, Atsushi Naganuma, Sohji Nishina, Motoyuki Otsuka, Taro Takami, Tetsuji Takayama, Takumi Kawaguchi, Hiroki Kawashima, Hepatology InVestigator Experts in Japan (HIVE-J) Study Group\",\"doi\":\"10.1111/hepr.14151\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Aim</h3>\\n \\n <p>Durvalumab plus tremelimumab (Dur/Tre) is a first-line systemic treatment option for unresectable hepatocellular carcinoma (uHCC). However, the management of severe immune-mediated adverse events (imAEs) is challenging. Therefore, we investigated the relationship between severe imAEs and antitumor responses in patients with uHCC treated with Dur/Tre.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>We included 157 patients with uHCC treated with Dur/Tre in this multicenter, retrospective study and analyzed the relationship between progression-free survival (PFS)/antitumor response and severe imAEs requiring high-dose corticosteroid treatment.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>Thirty-two patients (20.4%) developed severe imAEs, including enterocolitis/diarrhea (<i>n</i> = 10), liver injury (<i>n</i> = 9), interstitial lung disease (<i>n</i> = 5), rashes (<i>n</i> = 4), cytokine-release syndrome/fever (<i>n</i> = 2), pancreatitis (<i>n</i> = 2), and others (<i>n</i> = 4) (median follow-up period, 6.8 months). Infliximab was administered in six patients with steroid-refractory enterocolitis. Although the objective response rate (ORR) and disease control rate (DCR) were significantly higher with first-line therapy than with later-line therapy (<i>p</i> = 0.026), the frequency of severe imAEs was not significantly different (<i>p</i> = 0.221). The ORR and DCR in patients with and without severe imAEs were 15.6% and 17.6% and 65.6% and 47.2%, respectively, with no significant differences. Five patients with severe imAEs, including rashes and liver injury, showed objective responses (partial response + complete response). Among patients who achieved an objective response, the PFS at 10 months was good (100% and 70.3% with and without high-dose corticosteroids, respectively).</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusions</h3>\\n \\n <p>Severe imAEs of Dur/Tre treatment requiring high-dose corticosteroid treatment did not affect antitumor efficacy, which differed depending on the type of imAEs. Therefore, appropriately managing imAEs is essential to guide sequential treatment.</p>\\n </section>\\n </div>\",\"PeriodicalId\":12987,\"journal\":{\"name\":\"Hepatology Research\",\"volume\":\"55 4\",\"pages\":\"577-587\"},\"PeriodicalIF\":3.4000,\"publicationDate\":\"2024-12-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hepr.14151\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Hepatology Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1111/hepr.14151\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"GASTROENTEROLOGY & HEPATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Hepatology Research","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/hepr.14151","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
Antitumor effects and immune-mediated adverse events of durvalumab plus tremelimumab treatment for unresectable hepatocellular carcinoma
Aim
Durvalumab plus tremelimumab (Dur/Tre) is a first-line systemic treatment option for unresectable hepatocellular carcinoma (uHCC). However, the management of severe immune-mediated adverse events (imAEs) is challenging. Therefore, we investigated the relationship between severe imAEs and antitumor responses in patients with uHCC treated with Dur/Tre.
Methods
We included 157 patients with uHCC treated with Dur/Tre in this multicenter, retrospective study and analyzed the relationship between progression-free survival (PFS)/antitumor response and severe imAEs requiring high-dose corticosteroid treatment.
Results
Thirty-two patients (20.4%) developed severe imAEs, including enterocolitis/diarrhea (n = 10), liver injury (n = 9), interstitial lung disease (n = 5), rashes (n = 4), cytokine-release syndrome/fever (n = 2), pancreatitis (n = 2), and others (n = 4) (median follow-up period, 6.8 months). Infliximab was administered in six patients with steroid-refractory enterocolitis. Although the objective response rate (ORR) and disease control rate (DCR) were significantly higher with first-line therapy than with later-line therapy (p = 0.026), the frequency of severe imAEs was not significantly different (p = 0.221). The ORR and DCR in patients with and without severe imAEs were 15.6% and 17.6% and 65.6% and 47.2%, respectively, with no significant differences. Five patients with severe imAEs, including rashes and liver injury, showed objective responses (partial response + complete response). Among patients who achieved an objective response, the PFS at 10 months was good (100% and 70.3% with and without high-dose corticosteroids, respectively).
Conclusions
Severe imAEs of Dur/Tre treatment requiring high-dose corticosteroid treatment did not affect antitumor efficacy, which differed depending on the type of imAEs. Therefore, appropriately managing imAEs is essential to guide sequential treatment.
期刊介绍：
Hepatology Research (formerly International Hepatology Communications) is the official journal of the Japan Society of Hepatology, and publishes original articles, reviews and short comunications dealing with hepatology. Reviews or mini-reviews are especially welcomed from those areas within hepatology undergoing rapid changes. Short communications should contain concise definitive information.
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