Adhoute Xavier, De Matharel Marie, Mineur Laurent, Pénaranda Guillaume, Ouizeman Dann, Toullec Clemence, Tran Albert, Castellani Paul, Rollet Armelle, Oules Valérie, Perrier Hervé, Si Ahmed Si Nafa, Bourliere Marc, Anty Rodolphe
Department of Gastroenterology and Hepatology, Hôpital Saint-Joseph, Marseille 13000, France.
Department of Gastroenterology and Hepatology, Hôpital Universitaire de l'Archet, Nice 06000, France.
World J Gastrointest Oncol. 2022 Aug 15;14(8):1510-1527. doi: 10.4251/wjgo.v14.i8.1510.
Starting a second-line systemic treatment for hepatocellular carcinoma (HCC) is a common situation. The only therapeutic options in France are two broad-spectrum tyrosine kinase inhibitors (TKIs), regorafenib (REG) and cabozantinib (CBZ), but no comparative real-life studies are available.
To evaluate the progression-free survival (PFS) of patients treated with REG or CBZ, we investigated the disease control rate (DCR), overall survival (OS), and safety of both drugs. To identify the variables associated with disease progression over time.
A retrospective multicenter study was performed on the clinical data of patients attending one of three referral centers (Avignon, Marseille, and Nice) between January 2017 and March 2021 using propensity score matching. PFS and OS were assessed using the Kaplan-Meier method. Multivariate analysis (MA) of progression risk factors over time was performed in matched-pair groups.
Fifty-eight patients 68 (62-74) years old with HCC, Barcelona clinic liver cancer (BCLC) B/C (86%), Child-Pugh (CP)-A/B (24%) received REG for 3.4 (1.4-10.5) mo as second-line therapy. Twenty-eight patients 68 (60-73) years, BCLC B/C (75%), CP-A/B (25%) received CBZ for 3.7 (1.8-4.9) mo after first-line treatment with sorafenib [3 (2-4) (CBZ) 4 (2.9-11.8) mo (REG), = 0.0226]. Twenty percent of patients received third-line therapy. After matching, PFS and DCR were not significantly different after a median follow-up of 6.2 (2.7-11.7) mo (REG) 5.2 (4-7.2) mo (CBZ), = 0.6925. There was no difference in grade 3/4 toxicities, dose reductions, or interruptions. The OS of CP-A patients was 8.3 (5.2-24.8) 4.9 (1.6-11.7) mo (CP-B), = 0.0468. The MA of risk factors for progression over time identified C-reactive protein (CRP) > 10 mg/L, neutrophil-to-lymphocyte ratio (NLR) > 3, and aspartate aminotransferase (AST) > 45 IU as predictive factors.
This multicenter indirect comparative study found no significant difference in PFS between REG and CBZ as second-line therapy for advanced HCC. Elevated levels of inflammatory markers (CRP and NLR) and AST were associated with non-control of TKIs over time. A 2-mo online progression risk calculation is proposed.
启动肝细胞癌（HCC）的二线全身治疗是一种常见情况。在法国，仅有的治疗选择是两种广谱酪氨酸激酶抑制剂（TKIs），即瑞戈非尼（REG）和卡博替尼（CBZ），但尚无比较性的真实世界研究。
为评估接受REG或CBZ治疗患者的无进展生存期（PFS），我们研究了两种药物的疾病控制率（DCR）、总生存期（OS）和安全性。以确定随时间推移与疾病进展相关的变量。
采用倾向得分匹配法，对2017年1月至2021年3月期间在三个转诊中心（阿维尼翁、马赛和尼斯）之一就诊的患者的临床数据进行回顾性多中心研究。使用Kaplan-Meier方法评估PFS和OS。在配对组中对随时间推移的进展危险因素进行多变量分析（MA）。
58例68（62 - 74）岁的HCC患者，巴塞罗那临床肝癌（BCLC）B/C期（86%），Child-Pugh（CP）-A/B级（24%）接受REG作为二线治疗3.4（1.4 - 10.5）个月。28例68（60 - 73）岁，BCLC B/C期（75%），CP-A/B级（25%）在接受索拉非尼一线治疗后接受CBZ治疗3.7（1.8 - 4.9）个月[3（2 - 4）（CBZ）对4（2.9 - 11.8）个月（REG），P = 0.0226]。20%的患者接受了三线治疗。匹配后，中位随访6.2（2.7 - 11.7）个月（REG）与5.2（4 - 7.2）个月（CBZ）后，PFS和DCR无显著差异，P = 0.6925。3/4级毒性、剂量减少或中断方面无差异。CP-A级患者的OS为8.3（5.2 - 24.8）个月对4.9（1.6 - 11.7）个月（CP-B级），P = 0.0468。随时间推移的进展危险因素的MA确定C反应蛋白（CRP）>10 mg/L、中性粒细胞与淋巴细胞比值（NLR）>3和天冬氨酸转氨酶（AST）>45 IU为预测因素。
这项多中心间接比较研究发现，REG和CBZ作为晚期HCC的二线治疗，PFS无显著差异。炎症标志物（CRP和NLR）和AST水平升高与TKIs随时间推移无法控制疾病相关。提出了一个2个月的在线进展风险计算方法。
