Wu Meng, Fulgenzi Claudia A M, D'Alessio Antonio, Cortellini Alessio, Celsa Ciro, Manfredi Giulia F, Stefanini Bernardo, Wu Y Linda, Huang Yi-Hsiang, Saeed Anwaar, Pirozzi Angelo, Pressiani Tiziana, Rimassa Lorenza, Schoenlein Martin, Schulze Kornelius, von Felden Johann, Mohamed Yehia, Kaseb Ahmed O, Vogel Arndt, Roehlen Natascha, Silletta Marianna, Nishida Naoshi, Kudo Masatoshi, Vivaldi Caterina, Balcar Lorenz, Scheiner Bernhard, Pinter Matthias, Singal Amit G, Glover Joshua, Ulahannan Susanna, Foerster Fredrich, Weinmann Arndt, Galle Peter R, Parikh Neehar D, Hsu Wei-Fan, Parisi Alessandro, Chon Hong Jae, Pinato David J, Ang Celina
Division of Hematology/Oncology, Department of Medicine, Tisch Cancer Institute, Mount Sinai Hospital, New York, NY, USA.
Division of Cancer, Department of Surgery and Cancer, Imperial College London, London, United Kingdom.
JHEP Rep. 2024 Oct 10;7(2):101232. doi: 10.1016/j.jhepr.2024.101232. eCollection 2025 Feb.
BACKGROUND & AIMS: Atezolizumab/bevacizumab (A/B) is now a standard first-line treatment for advanced hepatocellular carcinoma (HCC), but the optimal second-line regimen is not known. We evaluated real-world treatment patterns and outcomes to investigate factors associated with post-progression survival (PPS).
In this multicenter, international, retrospective study, we examined clinical characteristics and outcomes of patients with advanced HCC who progressed on first-line A/B. The primary outcome of PPS was defined as time from first radiographic progression on A/B to death.
A total of 406 patients alive after progression on first-line A/B were included in the final analysis, of whom 45.3% (n = 184) received best supportive treatment (BST) and 54.7% (n = 222) continued active systemic treatment. In the second line, 155 patients were treated with tyrosine kinase inhibitors (TKIs), 45 with immune checkpoint inhibitor (IO)-based regimens, and 3 had missing data. Median PPS of the whole cohort (mPPS) was 6.0 months (95% CI 5.2-7.2). On multivariate Cox regression analysis, absence of portal vein tumor thrombus, ECOG <2, and continued active treatment were predictors of better PPS. mPPS was significantly longer for patients who continued active treatment BST (9.7 2.6 months; HR 0.41, 0.001). In the second-line setting, patients treated with TKIs had a numerically shorter mPPS compared to those treated with IO (8.4 14.9 months; HR 1.37, 0.256).
Continuation of active therapy after A/B progression was independently associated with better survival even after adjusting for baseline disease characteristics. mPPS with IO-based therapy exceeded a year, suggesting that IO continuation post-progression may retain benefit. The precise sequencing of TKI and IO regimens warrants further investigation.
There is currently a lack of level 1 data on second-line treatment options for patients with advanced hepatocellular carcinoma who progress after frontline atezolizumab plus bevacizumab, as all second-line approvals were established during the frontline sorafenib era. Our study aims to fill in some of the knowledge gap by investigating real-world patient outcomes in the second-line treatment setting. Findings from this study show that patients who continued active treatment had improved post-progression survival compared to those who received best supportive care, and medication regimens incorporating tyrosine kinase inhibitors as well as immunotherapy agents were active. These results can help inform clinicians of possible treatment options for patients who progress after frontline atezolizumab plus bevacizumab while we await maturing data from randomized-controlled trials.
阿替利珠单抗/贝伐珠单抗（A/B）目前是晚期肝细胞癌（HCC）的标准一线治疗方案，但最佳二线治疗方案尚不清楚。我们评估了真实世界的治疗模式和结局，以研究与进展后生存期（PPS）相关的因素。
在这项多中心、国际性、回顾性研究中，我们检查了一线A/B治疗后病情进展的晚期HCC患者的临床特征和结局。PPS的主要结局定义为从A/B首次影像学进展到死亡的时间。
共有406例一线A/B治疗后病情进展仍存活的患者纳入最终分析，其中45.3%（n = 184）接受了最佳支持治疗（BST），54.7%（n = 222）继续进行积极的全身治疗。二线治疗中，155例患者接受了酪氨酸激酶抑制剂（TKIs）治疗，45例接受了基于免疫检查点抑制剂（IO）的方案治疗，3例数据缺失。整个队列的中位PPS（mPPS）为6.0个月（95%CI 5.2 - 7.2）。多因素Cox回归分析显示，无门静脉肿瘤血栓、东部肿瘤协作组（ECOG）评分<2以及继续积极治疗是PPS较好的预测因素。继续积极治疗的患者的mPPS显著长于接受BST的患者（9.7对2.6个月；风险比[HR] 0.41，P < 0.001）。在二线治疗中，接受TKIs治疗的患者的mPPS在数值上短于接受IO治疗的患者（8.4对14.9个月；HR 1.37，P = 0.256）。
即使在调整基线疾病特征后，A/B进展后继续积极治疗与更好的生存率独立相关。基于IO治疗的mPPS超过1年，表明进展后继续使用IO可能仍有益处。TKI和IO方案的精确序贯治疗值得进一步研究。
目前缺乏关于一线阿替利珠单抗加贝伐珠单抗治疗后病情进展的晚期肝细胞癌患者二线治疗选择的1级数据，因为所有二线治疗的批准都是在一线索拉非尼时代确定的。我们的研究旨在通过调查二线治疗环境中真实世界患者的结局来填补一些知识空白。这项研究的结果表明，与接受最佳支持治疗的患者相比，继续积极治疗的患者进展后生存期有所改善，并且包含酪氨酸激酶抑制剂以及免疫治疗药物的治疗方案是有效的。在我们等待随机对照试验的成熟数据时，这些结果可以帮助临床医生了解一线阿替利珠单抗加贝伐珠单抗治疗后病情进展的患者可能的治疗选择。
