Department of Gastroenterology, Hepatobiliary and Pancreatic Medical Oncology Division, Kanagawa Cancer Center, Nakao 2-3-2, Asahi-ku, Yokohama, Kanagawa, 241-8515, Japan.
Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Kanagawa, Japan.
BMC Cancer. 2022 May 7;22(1):517. doi: 10.1186/s12885-022-09625-x.
Transarterial chemoembolization (TACE) is the standard treatment for intermediate stage hepatocellular carcinoma (HCC) (Barcelona Clinic Liver Cancer [BCLC] B). However, it often leads to a poor prognosis and decreased hepatic function especially in patients with BCLC substage B2. Lenvatinib (LEN) was demonstrated to be efficacious in these patients in the REFLECT phase 3 trial. We therefore aimed to evaluate the efficacy and safety of LEN as a first-line treatment for the patients with HCC at BCLC substage B2.
This prospective observational study used LEN in TACE-naïve patients with HCC at BCLC substage B2 and preserved hepatic function. The primary endpoint was overall survival. A one-year survival rate threshold of 60% and an expected survival rate of 78%, based on previous reports of TACE, was assumed for setting the sample size. With a one-sided α-type error of 5% and 70% detection power, 25 patients were required over a 2-year enrollment period and 10-month follow-up period.
Thirty-one patients were enrolled in this study from June 2018 to June 2020. The 1-year survival rate was 71.0% (90% confidence interval, 68.4-73.6%). Median overall and progression-free survival periods were 17.0 and 10.4 months, and the objective response rates according to Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1 and modified RECIST criteria were 22.6% and 70.0%, respectively. Common adverse events (AEs) were fatigue (68%), hypertension (65%), anorexia (61%), palmar-plantar erythrodysesthesia (39%), and thrombocytopenia (32%) of any grade; aspartate aminotransferase increased (23%), alanine aminotransferase increased (16%), and grade ≥ 3 proteinuria (13%). Treatment interruption and dose reduction were required in 61% and 81% of patients, respectively. LEN was discontinued in 29 patients due to disease progression (n = 17), AEs (n = 9), conversion to curative treatments (n = 2), and sudden death (n = 1), whereas post-LEN treatments were administered in 18 patients, including systemic chemotherapy (n = 11), TACE (n = 6), transarterial infusion (n = 1) and clinical trial (n = 1).
The results suggest that LEN provides treatment benefits as an initial therapeutic in patients with BCLC substage B2 HCC with a safety profile comparable to that previously reported.
经动脉化疗栓塞术（TACE）是治疗中期肝细胞癌（HCC）（巴塞罗那临床肝癌[BCLC] B 期）的标准治疗方法。然而，它常常导致预后不良和肝功能下降，尤其是在 BCLC 亚期 B2 的患者中。仑伐替尼（LEN）在 REFLECT 三期临床试验中显示对这些患者有效。因此，我们旨在评估 LEN 作为 BCLC 亚期 B2 HCC 患者一线治疗的疗效和安全性。
这项前瞻性观察性研究使用 LEN 治疗 BCLC 亚期 B2 且肝功能保存的 HCC 初治患者。主要终点是总生存期。基于 TACE 的既往报告，设定了一个 60%的一年生存率阈值和 78%的预期生存率，以确定样本量。单侧 α 型错误为 5%，检测能力为 70%，需要在 2 年的入组期和 10 个月的随访期内招募 25 名患者。
本研究于 2018 年 6 月至 2020 年 6 月期间共纳入 31 名患者。1 年生存率为 71.0%（90%置信区间，68.4-73.6%）。中位总生存期和无进展生存期分别为 17.0 个月和 10.4 个月，根据实体瘤反应评估标准 1.1（RECIST）和改良 RECIST 标准的客观缓解率分别为 22.6%和 70.0%。常见的不良事件（AE）为乏力（68%）、高血压（65%）、厌食（61%）、掌跖红斑感觉迟钝（39%）和血小板减少（32%）的任何级别；天门冬氨酸氨基转移酶升高（23%）、丙氨酸氨基转移酶升高（16%）和≥3 级蛋白尿（13%）。需要中断治疗和降低剂量的患者分别占 61%和 81%。由于疾病进展（n=17）、AE（n=9）、转为治愈性治疗（n=2）和猝死（n=1），29 名患者停止使用 LEN，而 18 名患者接受了 LEN 后治疗，包括全身化疗（n=11）、TACE（n=6）、经动脉输注（n=1）和临床试验（n=1）。
结果表明，LEN 为 BCLC 亚期 B2 HCC 患者提供了治疗益处，安全性与既往报道相似。
