Lenvatinib单药治疗在HCC一线治疗中显示出疗效

StephenW

Lenvatinib Monotherapy Demonstrates Efficacy in the First Line for HCC
January 16, 2021
Dylann Cohn-Emery

In a retrospective, real-world analysis of patients with unresectable hepatocellular carcinoma in the United States, investigators observed that lenvatinib alone was effective as first-line treatment.

In a retrospective, real-world analysis of patients with unresectable hepatocellular carcinoma (uHCC) in the United States, investigators observed that lenvatinib (Lenvima) alone was effective as first-line treatment.1

“Real-world data are essential to assess if this efficacy translates into effectiveness in clinical practice,” the authors wrote in their background. “The main objective of our real-world data study was to assess clinical characteristics and effectiveness of lenvatinib among patients treated in United states clinical practices.”

With a median follow-up of 9 months after patients were diagnosed with HCC, the median progression-free survival (PFS) and overall survival (OS) with lenvatinib, an oral multikinase inhibitor, were not reached in the subgroups of patients with Child-Pugh class A (n = 104) and B (n = 91) or in the overall cohort (n = 233).

The landmark PFS was 85% at 6 months and 65% at 12 months in the overall cohort. For patients with Child-Pugh A disease, landmark PFS was 83% and 51% at 6 and 12 months, respectively; with Child-Pugh B disease, PFS was 90% and 76%, respectively.

At 6 and 12 months, the landmark OS in the overall cohort was 92% and 73%, respectively. Child-Pugh A landmark OS was 96% and 73% and Child-Pugh B was 90% and 78% at 6 and 12 months, respectively.

The provider-reported best response was complete response (CR) in 21% of patients in the overall cohort, partial response (PR) in 44%, and stable disease (SD) in 26%. Eight percent of patients in this cohort experienced disease progression and 1% of patients had unknown response.

Based on RECIST 1.1 (n = 125), the best response was CR in 16%, PR in 54%, and SD in 26%; 5% had disease progression. For the 11 patients evaluated with mRECIST, best response was CR in 73%, PR in 0%, and SD in 18%; 9% experienced disease progression.

At initiation, the median dose of lenvatinib was 12 mg, which was the dose used in the registration trial that led to lenvatinib’s approval. Lenvatinib was approved as monotherapy in patients with uHCC in August 2018 based on the phase 3 REFLECT trial (NCT01761266).2 Nine percent of patients required a dose reduction in the real-world data analysis.

The median duration of treatment with the study drug was 6.7 months after a median follow-up period of 9.1 months. Those remaining on lenvatinib by the end of follow-up made up 61% of patients.

After treatment with lenvatinib, the median time to second-line therapy was 7.8 months. There were 32 patients who started second-line treatment, with the most common being immunotherapy in 50%, sorafenib (Nexavar) in 31%, and regorafenib (Stivarga) in 9%.

Of the 233 patients treated with lenvatinib in the first line, a majority were Barcelona Clinical Liver Cancer stage B or C at initiation (28.8% and 43.8%, respectively). There were 18.5% of patients who exhibited portal vein invasion, of which 7% had main portal vein involvement.

Furthermore, 44.6% were reported to be Child-Pugh class A at initiation and 39.1% were Child-Pugh class B. Hepatitis C was reported in 36.1% of patients and 15.5% were reported to have hepatitis B. Patients with alcohol-related liver disease made up 28.3% of the overall cohort and 13.7% had nonalcoholic steatohepatitis.

Prior to initiation of lenvatinib, 20.2% of patients had procedures, the most common of which were transarterial chemoembolization in 10.7% and radiofrequency ablation in 8%.

The investigators included patients who started lenvatinib monotherapy in the first line between August 16, 2018 and September 30, 2019 in this retrospective analysis. Patients had to be 18 years or older with confirmed uHCC, and an ECOG performance status of 0 or 1.

If patients had evidence of other malignant neoplasms before their diagnosis of HCC, and if they had been disease free for over 3 years at the time of starting lenvatinib, they were not included in these data. Those who had liver transplantation at any point were also excluded.

For this analysis, the investigators recruited 75 physicians; 41.3% were from cancer centers, 37.3% were from private hospitals, and 17.3% were from academic teaching hospitals. They used data extracted from electronic health records of individual patients from the participating prescribing physicians.

No safety data were collected for this analysis.

Reference:

1. Singal AG, Nagar S, Hitchens A, Iyer S. Real-world effectiveness of lenvatinib monotherapy among unresectable hepatocellular carcinoma patients treated in United States clinical practices. Poster presented at: 2021 Gastrointestinal Cancers Symposium; January 15-17, 2021; virtual. Abstract 273.

2. FDA approves lenvatinib for unresectable hepatocellular carcinoma. News release. FDA, Published August 16, 2018. Accessed January 15, 2021. https://bit.ly/3snAcjT

StephenW

Lenvatinib单药治疗在HCC一线治疗中显示出疗效
2021年1月16日
迪兰·科恩·埃默里

在对美国不可切除的肝细胞癌患者进行的回顾性，现实世界分析中，研究人员观察到单独的lenvatinib作为一线治疗是有效的。

在对美国不可切除的肝细胞癌（uHCC）患者进行的回顾性，现实世界分析中，研究人员观察到单独的lenvatinib（Lenvima）可以作为一线治疗有效。1

作者在背景中写道：“真实数据对于评估这种功效是否转化为临床实践的有效性至关重要。” “我们现实世界数据研究的主要目标是评估在美国临床实践中接受治疗的患者中lenvatinib的临床特征和有效性。”

对儿童确诊为HCC的患者进行9个月的中位随访后，未达到口服多激酶抑制剂lenvatinib的中位无进展生存期（PFS）和总体生存期（OS）。 Pugh A级（n = 104）和B级（n = 91）或整个队列（n = 233）。

在整个队列中，标志性PFS在6个月时为85％，在12个月时为65％。对于患有Child-Pugh A病的患者，在6个月和12个月时，标志性PFS分别为83％和51％。患有Child-Pugh B病的PFS分别为90％和76％。

在第6和12个月时，总体队列中的标志性OS分别为92％和73％。 Child-Pugh A在6个月和12个月时的OS分别为96％和73％，Child-Pugh B分别为90％和78％。

提供者报告的最佳反应是总队列中21％的患者完全反应（CR），44％的部分反应（PR）和26％的稳定疾病（SD）。该队列中有8％的患者经历了疾病进展，并且有1％的患者有未知的反应。

根据RECIST 1.1（n = 125），最佳响应是CR占16％，PR占54％，SD占26％。 5％有疾病进展。对于11名接受mRECIST评估的患者，最佳反应为CR占73％，PR占0％，SD占18％。 9％的人经历了疾病进展。

刚开始时，lenvatinib的中位剂量为12 mg，这是注册试验中获得lenvatinib批准的剂量。根据3期REFLECT试验（NCT01761266），Lenvatinib于2018年8月被批准用于uHCC患者的单药治疗.2在现实世界的数据分析中，有9％的患者需要减少剂量。

中位随访时间为9.1个月后，研究药物的中位治疗时间为6.7个月。随访结束后仍在接受lenvatinib治疗的患者占61％。

接受lenvatinib治疗后，接受二线治疗的中位时间为7.8个月。有32例患者开始二线治疗，最常见的是50％的免疫疗法，索拉非尼（Nexavar）的31％和瑞格非尼（Stivarga）的9％。

在第一线接受lenvatinib治疗的233位患者中，大多数患者在开始时为巴塞罗那临床肝癌B期或C期（分别为28.8％和43.8％）。有18.5％的患者表现出门静脉侵犯，其中7％的患者主要累及门静脉。

此外，据报道有44.6％的儿童在开始时为Child-Pugh A级，39.1％为Child-Pugh的B级。据报告，丙型肝炎在36.1％的患者中报告，而15.5％的患者是B型肝炎。该病占总队列的28.3％，非酒精性脂肪性肝炎占13.7％。

在开始使用lenvatinib之前，有20.2％的患者接受了手术，其中最常见的是经动脉化学栓塞治疗的发生率为10.7％，而射频消融的发生率为8％。

在这项回顾性分析中，研究人员包括在2018年8月16日至2019年9月30日的第一线开始使用lenvatinib单药治疗的患者。患者必须年满18岁或以上且确诊uHCC，ECOG表现状态为0或1。

如果患者在诊断为HCC之前有其他恶性肿瘤的迹象，并且在开始使用lenvatinib时已有3年以上没有疾病，则这些数据将不包括在内。任何时候进行肝移植的人也被排除在外。

为了进行此分析，研究人员招募了75位医生；来自癌症中心的占41.3％，来自私立医院的占37.3％，来自学术教学医院的占17.3％。他们使用了从参与处方医生的单个患者的电子健康记录中提取的数据。

没有为该分析收集安全数据。

参考：

1. Singal AG，Nagar S，Hitchens A，IyerS。在美国临床实践中，lenvatinib单一疗法在不可切除的肝细胞癌患者中的实际疗效。海报发表于：2021年胃肠道癌专题讨论会； 2021年1月15日至17日；虚拟。摘要273。
2. FDA批准lenvatinib用于不可切除的肝细胞癌。 新闻发布。 FDA，2018年8月16日发布.2021年1月15日访问.https：//bit.ly/3snAcjT