仑伐替尼在临床实践中治疗不可切除肝细胞癌的潜力：多中心分析

Therapeutic potential of lenvatinib for unresectable hepatocellular carcinoma in clinical practice: Multicenter analysis.

作者信息

Hiraoka Atsushi, Kumada Takashi, Kariyama Kazuya, Takaguchi Koichi, Itobayashi Ei, Shimada Noritomo, Tajiri Kazuto, Tsuji Kunihiko, Ishikawa Toru, Ochi Hironori, Hirooka Masashi, Tsutsui Akemi, Shibata Hiroshi, Tada Toshifumi, Toyoda Hidenori, Nouso Kazuhiro, Joko Kouji, Hiasa Yoichi, Michitaka Kojiro

机构信息

Gastroenterology Center, Ehime Prefectural Central Hospital, Ehime, Japan.

Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Gifu, Japan.

出版信息

Hepatol Res. 2019 Jan;49(1):111-117. doi: 10.1111/hepr.13243. Epub 2018 Oct 9.

DOI:10.1111/hepr.13243

PMID:30144256

Abstract

AIM

Lenvatinib (LEN) has recently become available as a first-line tyrosine-kinase inhibitor (TKI) for unresectable hepatocellular carcinoma (u-HCC). In patients who showed intolerability or failure in other TKI treatments, alternative treatment options are needed. This retrospective study evaluated the therapeutic potential of LEN in clinical practice.

METHODS

We enrolled 57 u-HCC patients treated with LEN from March to June 2018. Lenvatinib was given orally to patients weighing <60 kg at 8 mg/day and at 12 mg/day to those ≥60 kg. Following the exclusion of patients whose initial LEN dose was reduced, 49 patients were evaluated in regard to their characteristics and early therapeutic response using modified Response Evaluation Criteria in Solid Tumors for findings of follow-up computed tomography (CT)/magnetic resonance imaging (MRI) examinations at 4 weeks after introducing LEN.

RESULTS

The average patient age was 72.4 ± 9.3 years and 38 (77.6%) were men. The LEN dose was 8 and 12 mg in 32 and 17 patients, respectively. Twenty-nine (59.2%) had history of treatment with sorafenib and six of them (20.7%) with regorafenib. Of the 49 patients, 27 were evaluated using findings obtained by enhanced CT/MRI at 4 weeks after introducing LEN. Partial response was shown in 11, stable disease in 12, and progressive disease in four (overall response rate [ORR], 40.7%; disease control rate [DCR], 85.2%). The ORR and DCR of TKI-naïve patients (n = 8) were 50.0% and 87.5%, respectively, whereas those of TKI-experienced patients (n = 19) were 36.8% and 84.2%, respectively (P = 0.675 and P = 1.00, respectively).

CONCLUSION

Early therapeutic response to LEN was favorable. This new TKI could have therapeutic potential both in patients with and without past TKI treatments.

摘要

目的

乐伐替尼（LEN）最近已成为不可切除肝细胞癌（u-HCC）的一线酪氨酸激酶抑制剂（TKI）。对于那些对其他TKI治疗不耐受或治疗失败的患者，需要其他治疗选择。这项回顾性研究评估了乐伐替尼在临床实践中的治疗潜力。

方法

我们纳入了2018年3月至6月接受乐伐替尼治疗的57例u-HCC患者。体重<60 kg的患者口服乐伐替尼的剂量为8 mg/天，体重≥60 kg的患者为12 mg/天。在排除初始乐伐替尼剂量降低的患者后，使用改良的实体瘤疗效评价标准，根据引入乐伐替尼4周后随访计算机断层扫描（CT）/磁共振成像（MRI）检查的结果，对49例患者的特征和早期治疗反应进行了评估。

结果

患者的平均年龄为72.4±9.3岁，38例（77.6%）为男性。32例和17例患者的乐伐替尼剂量分别为8 mg和12 mg。29例（59.2%）有索拉非尼治疗史，其中6例（20.7%）有瑞戈非尼治疗史。在这49例患者中，27例根据引入乐伐替尼4周后增强CT/MRI的结果进行评估。部分缓解11例，疾病稳定12例，疾病进展4例（总缓解率[ORR]为40.7%；疾病控制率[DCR]为85.2%）。初治TKI患者（n = 8）的ORR和DCR分别为50.0%和87.5%，而经治TKI患者（n = 19）的ORR和DCR分别为36.8%和84.2%（P分别为0.675和1.00）。