Takaki Shintaro, Kurosaki Masayuki, Mori Nami, Tsuji Keiji, Ochi Hironori, Marusawa Hiroyuki, Nakamura Shinichiro, Tada Toshifumi, Narita Ryoichi, Uchida Yasushi, Akahane Takehiro, Kondo Masahiko, Kusakabe Atsunori, Furuta Koichiro, Kobashi Haruhiko, Arai Hirotaka, Nonogi Michiko, Tamada Takashi, Hasebe Chitomi, Ogawa Chikara, Sato Takashi, Tamaki Nobuharu, Yasui Yutaka, Tsuchiya Kaoru, Izumi Namiki
Department of Gastroenterology, Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital, Hiroshima, Japan.
Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan.
Invest New Drugs. 2023 Apr;41(2):340-349. doi: 10.1007/s10637-023-01349-4. Epub 2023 Mar 30.
This study aimed to describe the real-world efficacy and safety of the combination therapy of atezolizumab and bevacizumab (Atezo/Bev) for unresectable hepatocellular carcinoma (HCC). This retrospective analysis of a multicenter registry cohort included 268 patients treated with Atezo/Bev. The incidence of adverse events (AE) and its impact on overall survival (OS) and progression-free survival (PFS) were analyzed. Of the 268 patients, 230 (85.8%) experienced AE. The median OS and PFS in the whole cohort were 462 and 239 days, respectively. The OS and PFS were not different in terms of AE, but they were significantly shorter in patients with increased bilirubin level and those with increased aspartate aminotransferase (AST) or alanine aminotransferase (ALT). Regarding increased bilirubin level, the hazard ratios (HRs) were 2.61 (95% confidence interval [CI]: 1.04-6.58, P = 0.042) and 2.85 (95% CI: 1.37-5.93, P = 0.005) for OS and PFS, respectively. Regarding increased AST or ALT, the HRs were 6.68 (95% CI: 3.22-13.84, P < 0.001) and 3.54 (95% CI: 1.83-6.86, P < 0.001) for OS and PFS, respectively. Contrarily, the OS was significantly longer in patients with proteinuria (HR: 0.46 [95% CI: 0.23-0.92], P = 0.027). Multivariate analysis confirmed that proteinuria (HR: 0.53 [95% CI: 0.25-0.98], P = 0.044) and increased AST or ALT (HR: 6.679 [95% CI: 3.223-13.84], P = 0.003) were independent risk factors for a shorter OS. Furthermore, analysis limited to cases who completed at least 4 cycles confirmed that increased AST or ALT and proteinuria were negative and positive factors for OS, respectively. In the real-world setting, increased AST or ALT and bilirubin level during Atezo/Bev treatment were found to have a negative impact on PFS and OS, whereas proteinuria had a positive impact on OS.
本研究旨在描述阿替利珠单抗和贝伐珠单抗联合治疗（阿替利珠单抗/贝伐珠单抗）用于不可切除肝细胞癌（HCC）的真实世界疗效和安全性。这项对多中心注册队列的回顾性分析纳入了268例接受阿替利珠单抗/贝伐珠单抗治疗的患者。分析了不良事件（AE）的发生率及其对总生存期（OS）和无进展生存期（PFS）的影响。在这268例患者中，230例（85.8%）发生了AE。整个队列的中位OS和PFS分别为462天和239天。AE方面的OS和PFS无差异，但胆红素水平升高的患者以及天冬氨酸转氨酶（AST）或丙氨酸转氨酶（ALT）升高的患者的OS和PFS显著缩短。关于胆红素水平升高，OS和PFS的风险比（HR）分别为2.61（95%置信区间[CI]：1.04 - 6.58，P = 0.042）和2.85（95%CI：1.37 - 5.93，P = 0.005）。关于AST或ALT升高，OS和PFS的HR分别为6.68（95%CI：3.22 - 13.84，P < 0.001）和3.54（95%CI：1.83 - 6.86，P < 0.001）。相反，蛋白尿患者的OS显著更长（HR：0.46 [95%CI：0.23 - 0.92]，P = 0.027）。多因素分析证实，蛋白尿（HR：0.53 [95%CI：0.25 - 0.98]，P = 0.044）和AST或ALT升高（HR：6.679 [95%CI：3.223 - 13.84]，P = 0.003）是OS缩短的独立危险因素。此外，仅限于完成至少4个周期的病例的分析证实，AST或ALT升高和蛋白尿分别是OS的负性和正性因素。在真实世界中，阿替利珠单抗/贝伐珠单抗治疗期间AST或ALT以及胆红素水平升高对PFS和OS有负面影响，而蛋白尿对OS有正面影响。
