Tanaka Takaaki, Hiraoka Atsushi, Tada Toshifumi, Hirooka Masashi, Kariyama Kazuya, Tani Joji, Atsukawa Masanori, Takaguchi Koichi, Itobayashi Ei, Fukunishi Shinya, Tsuji Kunihiko, Ishikawa Toru, Tajiri Kazuto, Ochi Hironori, Yasuda Satoshi, Toyoda Hidenori, Ogawa Chikara, Nishimura Takashi, Hatanaka Takeshi, Kakizaki Satoru, Shimada Noritomo, Kawata Kazuhito, Naganuma Atsushi, Kosaka Hisashi, Ohama Hideko, Nouso Kazuhiro, Morishita Asahiro, Tsutsui Akemi, Nagano Takuya, Itokawa Norio, Okubo Tomomi, Arai Taeang, Imai Michitaka, Koizumi Yohei, Nakamura Shinichiro, Joko Kouji, Iijima Hiroko, Kaibori Masaki, Hiasa Yoichi, Kudo Masatoshi, Kumada Takashi
Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan.
Department of Internal Medicine, Japanese Red Cross Himeji Hospital, Himeji, Japan.
Hepatol Res. 2022 Sep;52(9):773-783. doi: 10.1111/hepr.13797. Epub 2022 Jun 11.
BACKGROUND/AIM: Atezolizumab plus bevacizumab (Atez/Bev) treatment is recommended for unresechepatocellular carcinoma (u-HCC) patients classified as Child-Pugh A (CP-A). This study aimed to elucidate the prognosis of patients treated with Atez/Bev, especially CP-A and -B cases.
MATERIALS/METHODS: From September 2020 to March 2022, 457 u-HCC patients treated with Atez/Bev were enrolled (median age 74 years, male:female = 368:89, CP-A:CP-B = 427:30, Child-Pugh score [CPS] 5:6:7:8:9 = 271:156:21:8:1). Therapeutic response was evaluated using RECIST ver.1.1. Clinical features and prognosis were retrospectively evaluated.
There were no significant differences between CP-A and -B patients in regard to best response (CR:PR:SD:PD = 16:91:194:81 vs. 0:7:13:8, p = 0.739; objective response rate/disease control rate = 28.0%/78.8% vs. 25.0%/71.4%). Analysis performed using inverse probability weighting adjustments of clinical factors other than those related to hepatic reserve function with a p value < 0.10 for comparisons between patients with CP-A and -B showed that the progression-free survival (PFS) rate for CP-A cases was better (6-/12-/18-month: 58.2%/36.1%/27.8% vs. 49.6%/8.7%/non-estimable [NE], p < 0.001), as was overall survival (OS) rate (6-/12-/18-month: 89.9%/71.7%/51.4% versus 63.6%/18.4%/NE; p < 0.001). Median PFS (mPFS) and median OS (mOS) for the CPS-5 were 9.5 months/NE, and 5.1/14.0 months for the CPS-6 (both p < 0.001). Furthermore, for modified albumin-bilirubin grade (mALBI)-1/2a/2b, mPFS was 9.4/8.5/5.3 months (p < 0.001) and mOS was NE/17.8/13.4 months (p < 0.001).
Better hepatic function, such as mALBI grade 1 or 2a are thought to indicate a better condition for obtaining sufficient prognosis with Atez/Bev treatment for u-HCC patients, whereas for CP-B patients, who mainly shown an mALBI grade of 2b or 3, Atez/Bev might have less therapeutic efficacy.
背景/目的：阿替利珠单抗联合贝伐珠单抗（阿替利珠单抗/贝伐珠单抗）治疗方案被推荐用于Child-Pugh A（CP-A）级的不可切除肝细胞癌（u-HCC）患者。本研究旨在阐明接受阿替利珠单抗/贝伐珠单抗治疗患者的预后情况，尤其是CP-A级和CP-B级病例。
材料/方法：2020年9月至2022年3月，纳入457例接受阿替利珠单抗/贝伐珠单抗治疗的u-HCC患者（中位年龄74岁，男:女 = 368:89，CP-A:CP-B = 427:30，Child-Pugh评分[CPS] 5:6:7:8:9 = 271:156:21:8:1）。使用RECIST 1.1版评估治疗反应。对临床特征和预后进行回顾性评估。
CP-A级和CP-B级患者在最佳反应方面无显著差异（完全缓解[CR]:部分缓解[PR]:疾病稳定[SD]:疾病进展[PD] = 16:91:194:81 vs. 0:7:13:8，p = 0.739；客观缓解率/疾病控制率 = 28.0%/78.8% vs. 25.0%/7其肝储备功能相关因素以外的临床因素进行逆概率加权调整分析，p值<0.10用于CP-A级和CP-B级患者之间的比较，结果显示CP-A级病例的无进展生存期（PFS）率更好（6/12/18个月：58.2%/36.1%/27.8% vs.
49.6%/8.7%/不可评估[NE]，p <
0.001），总生存期（OS）率也是如此（6/12/18个月：89.9%/71.7%/51.4% 对63.6%/18.4%/NE；p <
0.001）。CPS-5的中位PFS（mPFS）和中位OS（mOS）分别为9.5个月/NE，CPS-6的为5.1/14.0个月（均p <
0.001）。此外，对于改良白蛋白-胆红素分级（mALBI）-1/2a/2b，mPFS分别为9.4/8.5/5.3个月（p <
0.001），mOS分别为NE/17.8/13.4个月（p <
0.001）。
肝功能较好，如mALBI 1级或2a级，被认为表明u-HCC患者接受阿替利珠单抗/贝伐珠单抗治疗获得充分预后的条件较好，而对于主要表现为mALBI 2b级或3级的CP-B级患者，阿替利珠单抗/贝伐珠单抗的治疗效果可能较差。
