晚期肝细胞癌系统治疗全程中甲胎蛋白的变化——一项真实世界、多中心研究
Changes in alpha-fetoprotein across the systemic therapy continuum in advanced hepatocellular carcinoma-a real-world, multicenter study.
作者信息
Li Michael, Hannan Lindsay M, Goyal Lipika, Bocobo Andrea G, Parks Anna L, Bauer Kelly, Baiev Islam, Dinicola Caroline, Gordan John D, Venook Alan P, Harris William P, Bracci Paige, Kelley Robin K
机构信息
Division of Gastroenterology and Hepatology, Department of Medicine, University of California, San Francisco. 513 Parnassus Ave, S-357, San Francisco, CA 94143, USA.
University of Washington Medical Center, Seattle, WA, USA.
出版信息
Ther Adv Med Oncol. 2024 Nov 19;16:17588359241297085. doi: 10.1177/17588359241297085. eCollection 2024.
BACKGROUND
Early changes in alpha-fetoprotein (AFP) are a promising surrogate endpoint for systemic treatment outcomes in hepatocellular carcinoma (HCC).
OBJECTIVES
We sought to investigate the utility of AFP response across first-line sorafenib (1L SOR) and later-line checkpoint inhibitor (CPI) therapies.
DESIGN
We conducted a multicenter, retrospective cohort study of patients with advanced HCC who received 1L SOR and any subsequent CPI.
METHODS
The primary outcomes were overall survival (OS) and time on treatment (TOT). Pre-treatment AFP and the lowest AFP within 3 months of treatment initiation were used to calculate the percent change in AFP for each treatment. AFP response was defined as an AFP reduction by ⩾20% within 3 months, and AFP progression was defined as an increase in AFP by ⩾20% within 3 months. Patients with baseline AFP < 20 ng/mL were considered not evaluable for AFP change.
RESULTS
Of 176 study patients, 46 (28%) received CPI after SOR, and 125 (71%) had a baseline AFP ⩾ 20. Patients who experienced AFP response on SOR had significantly longer OS and TOT than those who did not and those who were not evaluable (OS: median 689 vs 320 vs 452 days, log-rank < 0.001; TOT: median log of days 5.2 vs 4.5 vs 4.9, < 0.001). Patients with AFP progression following SOR had significantly shorter OS than those who did not and those who were not evaluable (median 304 vs 557 vs 452, log-rank = 0.008). Similarly, patients with AFP response following CPI therapy had a significantly reduced risk of death compared with those who did not have an AFP response (hazard ratio 0.13, 95% confidence interval 0.03-0.60, = 0.009).
CONCLUSION
Early AFP response with 1L SOR and any subsequent CPI was associated with longer OS and TOT, and early AFP progression was associated with shorter OS and TOT. These data support utilizing longitudinal AFP changes as a surrogate endpoint in HCC systemic therapy.
背景
甲胎蛋白（AFP）的早期变化是肝细胞癌（HCC）全身治疗效果的一个很有前景的替代终点。
目的
我们试图研究AFP反应在一线索拉非尼（1L SOR）和二线检查点抑制剂（CPI）治疗中的效用。
设计
我们对接受1L SOR及任何后续CPI治疗的晚期HCC患者进行了一项多中心回顾性队列研究。
方法
主要结局是总生存期（OS）和治疗时间（TOT）。治疗开始前的AFP水平和治疗开始后3个月内的最低AFP水平用于计算每次治疗的AFP变化百分比。AFP反应定义为3个月内AFP降低≥20%，AFP进展定义为3个月内AFP升高≥20%。基线AFP<20 ng/mL的患者被认为无法评估AFP变化。
结果
在176例研究患者中，46例（28%）在索拉非尼治疗后接受了CPI治疗，125例（71%）基线AFP≥20。在索拉非尼治疗中出现AFP反应的患者的OS和TOT显著长于未出现反应的患者以及无法评估的患者（OS：中位数689天对320天对452天，对数秩检验<0.001；TOT：天数对数中位数5.2对4.5对4.9，<0.001）。索拉非尼治疗后出现AFP进展的患者的OS显著短于未出现进展的患者以及无法评估的患者（中位数304天对557天对452天，对数秩检验=0.008）。同样，CPI治疗后出现AFP反应的患者与未出现AFP反应的患者相比，死亡风险显著降低（风险比0.13，95%置信区间0.03 - 0.60，=0.009）。
结论
1L SOR及任何后续CPI治疗后的早期AFP反应与更长的OS和TOT相关，早期AFP进展与更短的OS和TOT相关。这些数据支持将纵向AFP变化作为HCC全身治疗的替代终点。
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