Tomonari Tetsu, Shimose Shigeo, Saeki Issei, Tani Joji, Honma Yuichi, Ito Takanori, Takeuchi Mamiko, Naito Takehito, Takeuchi Yasuto, Sasaki Ryu, Sasaki Kyo, Hatanaka Takeshi, Kakizaki Satoru, Kanayama Yuki, Naganuma Atsushi, Tanabe Norikazu, Tanaka Hironori, Kawano Yutaka, Sato Yasushi, Nishina Sohji, Miyaaki Hisamitsu, Otsuka Motoyuki, Kawashima Hiroki, Harada Masaru, Kobara Hideki, Takami Taro, Kawaguchi Takumi, Takayama Tetsuji
Department of Gastroenterology and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School of Medicine, Tokushima, Japan.
Tomonari Gastroenterology and Hepatology Clinic, Tokushima, Japan.
Hepatol Res. 2025 Aug;55(8):1184-1192. doi: 10.1111/hepr.14212. Epub 2025 May 28.
This study aimed to evaluate the efficacy of durvalumab + tremelimumab (Dur + Tre) in real-world clinical practice, characterize "stable disease (SD)," and identify SD responders (SD-R) who benefit from Dur + Tre treatment.
This multicenter observational study included 212 patients with unresectable hepatocellular carcinoma (u-HCC) treated with Dur + Tre between March 2023 and November 2024. The patients were categorized into 95 first-line and 117 later-line cases, respectively. Sequential cutoff points for depth of response (DOR) and progression-free survival (PFS) were tested to identify subgroups with survival outcomes comparable to those of responders.
Disease control rate (DCR) and PFS were significantly better in the first-line setting for both response evaluation criteria in solid tumors (RECIST) and modified RECIST (mRECIST) criteria. Patients who achieved PFS of ≥84 days or RECIST DOR of ≤-10% were classified as SD-R, as they had long-term survival outcomes similar to those with PR or CR. Furthermore, the CR + PR + SD-R group had significantly better survival outcomes than the other groups (p < 0.01), and multivariate analysis confirmed that SD-R was an independent prognostic factor with the strongest impact on survival outcomes (hazard ratio = 0.11).
In real-world clinical practice, Dur + Tre is highly effective as a first-line treatment for u-HCC. Additionally, patients with SD who met the SD-R criteria (PFS ≥84 days or RECIST DOR ≤-10%) showed survival outcomes comparable to those of patients with PR or CR. These findings may help identify patients who are most likely to benefit from treatment and improve their prognoses.
本研究旨在评估度伐利尤单抗+曲美木单抗（Dur+Tre）在真实世界临床实践中的疗效，对“疾病稳定（SD）”进行特征描述，并识别从Dur+Tre治疗中获益的SD反应者（SD-R）。
这项多中心观察性研究纳入了2023年3月至2024年11月期间接受Dur+Tre治疗的212例不可切除肝细胞癌（u-HCC）患者。患者分别分为95例一线病例和117例二线病例。对反应深度（DOR）和无进展生存期（PFS）的连续截断点进行测试，以识别生存结果与反应者相当的亚组。
在实体瘤疗效评价标准（RECIST）和改良RECIST（mRECIST）标准的一线治疗中，疾病控制率（DCR）和PFS均显著更好。达到PFS≥84天或RECIST DOR≤-10%的患者被归类为SD-R，因为他们的长期生存结果与PR或CR患者相似。此外，CR+PR+SD-R组的生存结果明显优于其他组（p<0.01），多变量分析证实SD-R是对生存结果影响最强的独立预后因素（风险比=0.11）。
在真实世界临床实践中，Dur+Tre作为u-HCC的一线治疗非常有效。此外，符合SD-R标准（PFS≥84天或RECIST DOR≤-10%）的SD患者的生存结果与PR或CR患者相当。这些发现可能有助于识别最有可能从治疗中获益的患者并改善其预后。
