Falette-Puisieux Manon, Nault Jean-Charles, Bouattour Mohamed, Lequoy Marie, Amaddeo Giuliana, Decaens Thomas, Di Fiore Frederic, Manfredi Sylvain, Merle Philippe, Baron Aurore, Locher Christophe, Pellat Anna, Coriat Romain
Gastroenterology and Digestive Oncology Unit, Cochin Hospital AP-HP, 27 rue du Faubourg Saint Jacques, Paris 75014, France.
Hepatology Unit, Hôpital Avicenne, Hôpitaux Universitaires Paris Seine-Saint-Denis, Assistance Publique-Hôpitaux de Paris, Bobigny, France.
Ther Adv Med Oncol. 2023 Aug 1;15:17588359231189425. doi: 10.1177/17588359231189425. eCollection 2023.
In patients with advanced hepatocellular carcinoma (HCC) progressing after atezolizumab and bevacizumab, the optimal therapeutic sequence is still unclear and no second-line agent has proven its efficacy.
The aim of this retrospective multicenter real-world cohort study was to provide an evaluation of the efficacy and safety of the use of second-line tyrosine kinase inhibitors (TKIs) in this population.
All patients with advanced HCC, treated in first-line setting by atezolizumab-bevacizumab, and who received at least one dose of treatment with TKI were included in this study. All the data were retrospectively collected from medical records. The primary outcome was progression-free survival (PFS). Secondary outcomes were overall survival (OS), overall global survival (OGS), and safety. A total of 82 patients were included in this study.
Patients were assigned to the regorafenib group ( = 29, 35.4%) or other TKI (sorafenib = 41, lenvatinib = 8, or cabozantinib = 4) group ( = 53). PFS was not significantly different between the two groups [2.6 2.8 months, HR 1.07 (95% CI: 0.61-1.86), = 0.818]. Median PFS rates were 2.6, 4.4, and 2.8 months in sorafenib-, lenvatinib-, and cabozantinib group, respectively. OS was statistically different between the regorafenib group and other TKI group [15.8 7.0 months, HR 0.40 (95% CI: 0.20-0.79), = 0.023]. When adjusting on confounding factors, there was still a difference in OS favoring the regorafenib group (adjusted hazard ratio 0.35, = 0.019). OGS of patients who received regorafenib was improved compared to other TKI [18.6 15.0 months, HR 0.42 (95% CI: 0.22-0.84), = 0.036]. Twenty percent of patients had grade 3 and none had grade 4 or 5 adverse events. In patients who experienced disease progression and fit for a third-line treatment, 80% and 50% received cabozantinib in regorafenib group and other TKI group, respectively.
Efficacy of any TKI in the second-line setting was not affected by atezolizumab-bevacizumab treatment as first-line therapy. The safety profile in the second-line setting was consistent with the results shown in pivotal studies. PFS rates of patients were similar, regardless of TKI type. Regorafenib was associated with better OS and OGS rates compared to other TKI. These data need to be confirmed in prospective comparative studies.
在接受阿替利珠单抗和贝伐单抗治疗后病情进展的晚期肝细胞癌（HCC）患者中，最佳治疗顺序仍不明确，且尚无二线药物证明其疗效。
这项回顾性多中心真实世界队列研究的目的是评估二线酪氨酸激酶抑制剂（TKIs）在该人群中的疗效和安全性。
本研究纳入了所有一线接受阿替利珠单抗-贝伐单抗治疗且至少接受过一剂TKI治疗的晚期HCC患者。所有数据均从病历中回顾性收集。主要结局是无进展生存期（PFS）。次要结局是总生存期（OS）、总体全球生存期（OGS）和安全性。本研究共纳入82例患者。
患者被分为瑞戈非尼组（n = 29，35.4%）或其他TKI组（索拉非尼n = 41，乐伐替尼n = 8，或卡博替尼n = 4）（n = 53）。两组之间的PFS无显著差异[2.6对2.8个月，HR 1.07（95%CI：0.61 - 1.86），P = 0.818]。索拉非尼组、乐伐替尼组和卡博替尼组的中位PFS率分别为2.6个月、4.4个月和2.8个月。瑞戈非尼组和其他TKI组之间的OS存在统计学差异[15.8对7.0个月，HR 0.40（95%CI：0.20 - 0.79），P = 0.023]。在调整混杂因素后，OS仍有利于瑞戈非尼组（调整后的风险比0.35，P = 0.019）。接受瑞戈非尼治疗的患者的OGS与其他TKI相比有所改善[18.6对15.0个月，HR 0.42（95%CI：0.22 - 0.84），P = 0.036]。20%的患者发生3级不良事件，无4级或5级不良事件。在经历疾病进展且适合三线治疗的患者中，瑞戈非尼组和其他TKI组分别有80%和50%的患者接受了卡博替尼治疗。
作为一线治疗，阿替利珠单抗-贝伐单抗治疗不影响任何TKI在二线治疗中的疗效。二线治疗的安全性与关键研究结果一致。无论TKI类型如何，患者的PFS率相似。与其他TKI相比，瑞戈非尼与更好的OS和OGS率相关。这些数据需要在前瞻性比较研究中得到证实。
