不可切除肝细胞癌患者接受仑伐替尼治疗后的进展后生存分析。
Analysis of Post-Progression Survival in Patients with Unresectable Hepatocellular Carcinoma Treated with Lenvatinib.
机构信息
Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Department of Gastroenterology, Hiroshima Red Cross Hospital and Atomic-Bomb Survivors Hospital, Hiroshima, Japan.
出版信息
Oncology. 2020;98(11):787-797. doi: 10.1159/000509387. Epub 2020 Sep 3.
BACKGROUND
Although a strong antitumor effect of lenvatinib (LEN) has been noted for patients with unresectable hepatocellular carcinoma (HCC), there are still no reports on the prognosis for patients with disease progression after first-line LEN therapy.
METHODS
Patients (n = 141) with unresectable HCC, Child-Pugh class A liver function, and an Eastern Cooperative Oncology Group performance status (ECOG-PS) of 0 or 1 who were treated with LEN from March 2018 to December 2019 were enrolled.
RESULTS
One hundred and five patients were treated with LEN as first-line therapy, 53 of whom had progressive disease (PD) at the radiological evaluation. Among the 53 patients with PD, there were 27 candidates for second-line therapy, who had Child-Pugh class A liver function and an ECOG-PS of 0 or 1 at progression. After progression on first-line LEN, 28 patients were treated with a molecular targeted agent (MTA) as second-line therapy (sorafenib: n = 26; ramucirumab: n = 2). Multivariate analysis identified modified albumin-bilirubin grade 1 or 2a at LEN initiation (odds ratio 5.18, 95% confidence interval [CI] 1.465-18.31, p = 0.011) as a significant and independent factor for candidates. The median post-progression survival after PD on first-line LEN was 8.3 months. Cox hazard multivariate analysis showed that a low alpha-fetoprotein level (<400 ng/mL; hazard ratio [HR] 0.297, 95% CI 0.099-0.886, p = 0.003), a relative tumor volume <50% at the time of progression (HR 0.204, 95% CI 0.07-0.592, p = 0.03), and switching to MTAs as second-line treatment after LEN (HR 0.299, 95% CI 0.12-0.746, p = 0.01) were significant prognostic factors.
CONCLUSION
Among patients with PD on first-line LEN, good liver function at introduction of LEN was an important and favorable factor related to eligibility for second-line therapy. In addition, post-progression treatment with MTAs could improve the prognosis for patients who had been treated with first-line LEN.
背景
仑伐替尼（LEN）在不可切除的肝细胞癌（HCC）患者中显示出很强的抗肿瘤作用，但对于一线 LEN 治疗后疾病进展的患者的预后，尚无报道。
方法
本研究纳入了 2018 年 3 月至 2019 年 12 月期间接受 LEN 治疗的不可切除 HCC、Child-Pugh 肝功能 A 级和东部合作肿瘤学组表现状态（ECOG-PS）为 0 或 1 的患者（n=141）。
结果
105 例患者接受 LEN 作为一线治疗，其中 53 例在影像学评估时发生疾病进展（PD）。在 53 例 PD 患者中，有 27 例候选二线治疗，这些患者在进展时具有 Child-Pugh 肝功能 A 级和 ECOG-PS 0 或 1。在一线 LEN 进展后，28 例患者接受了分子靶向药物（MTA）作为二线治疗（索拉非尼：n=26；雷莫芦单抗：n=2）。多变量分析确定 LEN 起始时改良的白蛋白-胆红素分级 1 或 2a（优势比 5.18，95%置信区间 [CI] 1.465-18.31，p=0.011）是候选患者的显著且独立的因素。一线 LEN 后 PD 后的中位无进展生存期为 8.3 个月。Cox 风险多变量分析显示，低甲胎蛋白水平（<400ng/mL；风险比 [HR] 0.297，95%CI 0.099-0.886，p=0.003）、进展时肿瘤相对体积<50%（HR 0.204，95%CI 0.07-0.592，p=0.03）和 LEN 后转换为 MTA 作为二线治疗（HR 0.299，95%CI 0.12-0.746，p=0.01）是显著的预后因素。
结论
在一线 LEN 治疗后发生 PD 的患者中，LEN 起始时良好的肝功能是与二线治疗资格相关的重要有利因素。此外，一线 LEN 治疗后使用 MTA 进行后续治疗可以改善患者的预后。
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