Gastroenterology Center, Ehime Prefectural Central Hospital, Kasuga-cho, Ehime, Japan.
Department of Nursing, Gifu Kyoritsu University, Ogaki, Japan.
Cancer Rep (Hoboken). 2022 Feb;5(2):e1464. doi: 10.1002/cnr2.1464. Epub 2021 Jun 11.
Although atezolizumab plus bevacizumab (Atez/bev) treatment has been developed for unresectable hepatocellular carcinoma (u-HCC), changes in hepatic function during therapy have yet to be reported.
This retrospective clinical study aimed to elucidate early responses to Atez/Bev.
From September 2020 to April 2021, 171 u-HCC patients undergoing Atez/Bev treatment were enrolled (BCLC stage A:B:C:D = 5:68:96:2). Of those, 75 had no prior history of systemic treatment. Relative changes in hepatic function and therapeutic response were assessed using albumin-bilirubin (ALBI) score and Response Evaluation Criteria in Solid Tumors (RECIST), ver. 1.1, respectively.
In initial imaging examination findings, objective response rates for early tumor shrinkage and disease control after 6 weeks (ORR-6W/DCR-6W) were 10.6%/79.6%. Similar response results were observed in patients with and without a past history of systemic treatment (ORR-6W/DCR-6W = 9.7%/77.8% and 12.2%/82.9%), as well as patients in whom Atez/Bev was used as post-progression treatment following lenvatinib (ORR-6W/DCR-6W = 7.7%/79.5%), for which no known effective post-progression treatment has been established. In 111 patients who underwent a 6-week observation period, ALBI score was significantly worsened at 3 weeks after introducing Atez/Bev (-2.525 ± 0.419 vs -2.323 ± 0.445, p < .001), but then recovered at 6-weeks (-2.403 ± 0.452) as compared to 3-weeks (p = .001). During the observation period, the most common adverse events were appetite loss (all grades) (12.3%), general fatigue/hypertension (all grades) (11.1%, respectively), and urine protein (all grades) (10.5%).
Atez/Bev might have therapeutic potential not only as first but also later-line treatment of existing molecular target agents. In addition, this drug combination may have less influence on hepatic function during the early period, as the present patients showed a good initial therapeutic response.
阿替利珠单抗联合贝伐珠单抗（Atez/bev）已被开发用于治疗不可切除的肝细胞癌（u-HCC），但目前尚不清楚治疗期间肝功能的变化情况。
本回顾性临床研究旨在阐明阿替利珠单抗联合贝伐珠单抗的早期应答情况。
2020 年 9 月至 2021 年 4 月，171 例接受 Atez/Bev 治疗的 u-HCC 患者入组（BCLC 分期 A：B：C：D=5：68：96：2）。其中，75 例患者无既往系统治疗史。采用白蛋白-胆红素（ALBI）评分和实体瘤反应评估标准（RECIST）1.1 分别评估治疗期间肝功能和治疗反应的相对变化。
在初始影像学检查结果中，6 周时早期肿瘤缩小的客观缓解率（ORR-6W）和疾病控制率（DCR-6W）分别为 10.6%和 79.6%。在有和无既往系统治疗史的患者中，以及在 lenvatinib 后进展时使用 Atez/Bev 作为后线治疗的患者中，也观察到类似的反应结果（ORR-6W/DCR-6W=9.7%/77.8%和 12.2%/82.9%，ORR-6W/DCR-6W=7.7%/79.5%），lenvatinib 尚无已知有效的后线治疗方案。在 111 例接受 6 周观察期的患者中，在开始使用 Atez/Bev 后 3 周时 ALBI 评分显著恶化（-2.525±0.419 比-2.323±0.445，p<0.001），但在 6 周时恢复（-2.403±0.452），与 3 周时相比差异有统计学意义（p=0.001）。在观察期间，最常见的不良事件为食欲下降（所有等级）（12.3%）、全身乏力/高血压（所有等级）（11.1%）和尿蛋白（所有等级）（10.5%）。
Atez/Bev 不仅可能作为现有分子靶向药物的一线治疗药物，也可能作为二线治疗药物具有治疗潜力。此外，由于本研究患者初始治疗应答良好，该药物联合方案在早期可能对肝功能的影响较小。
