Michael Li, Lindsay M Hannan, Lipika Goyal, Andrea G Bocobo, Anna L Parks, Kelly Bauer, Islam Baiev, Caroline Dinicola, John D Gordan, Alan P Venook, William P Harris, Paige Bracci, Robin K Kelley
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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.</p><p><strong>Results: </strong>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 <i>p</i> < 0.001; TOT: median log of days 5.2 vs 4.5 vs 4.9, <i>p</i> < 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 <i>p</i> = 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, <i>p</i> = 0.009).</p><p><strong>Conclusion: </strong>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. 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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.</p><p><strong>Results: </strong>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 <i>p</i> < 0.001; TOT: median log of days 5.2 vs 4.5 vs 4.9, <i>p</i> < 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 <i>p</i> = 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, <i>p</i> = 0.009).</p><p><strong>Conclusion: </strong>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. 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引用次数: 0
摘要
背景：甲胎蛋白（AFP）的早期变化是肝细胞癌（HCC）全身治疗效果的替代终点：甲胎蛋白（AFP）的早期变化是肝细胞癌（HCC）全身治疗结果的一个有希望的替代终点：我们试图研究甲胎蛋白反应在一线索拉非尼（1L SOR）和二线检查点抑制剂（CPI）疗法中的作用：我们对接受 1L SOR 和任何后续 CPI 治疗的晚期 HCC 患者进行了一项多中心、回顾性队列研究：主要结果是总生存期（OS）和治疗时间（TOT）。治疗前的 AFP 和治疗开始后 3 个月内的最低 AFP 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下降⩾20%，AFP进展定义为3个月内AFP上升⩾20%。基线 AFP 结果的患者：在 176 名研究患者中，46 人（28%）在 SOR 后接受了 CPI，125 人（71%）的基线 AFP ⩾20。SOR后出现AFP反应的患者的OS和TOT明显长于未出现反应和无法评估的患者（OS：中位689天 vs 320天 vs 452天，log-rank p p = 0.008）。同样，与未出现 AFP 反应的患者相比，CPI 治疗后出现 AFP 反应的患者死亡风险显著降低（危险比 0.13，95% 置信区间 0.03-0.60，P = 0.009）：结论：早期AFP反应（1L SOR及随后的CPI）与较长的OS和TOT相关，而早期AFP进展与较短的OS和TOT相关。这些数据支持将纵向 AFP 变化作为 HCC 系统治疗的替代终点。
Changes in alpha-fetoprotein across the systemic therapy continuum in advanced hepatocellular carcinoma-a real-world, multicenter study.
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 p < 0.001; TOT: median log of days 5.2 vs 4.5 vs 4.9, p < 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 p = 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, p = 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.
期刊介绍：
Therapeutic Advances in Medical Oncology is an open access, peer-reviewed journal delivering the highest quality articles, reviews, and scholarly comment on pioneering efforts and innovative studies in the medical treatment of cancer. The journal has a strong clinical and pharmacological focus and is aimed at clinicians and researchers in medical oncology, providing a forum in print and online for publishing the highest quality articles in this area. This journal is a member of the Committee on Publication Ethics (COPE).
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