Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan.
Department of Internal Medicine, Himeji Red Cross Hospital, Hyogo, Japan.
Invest New Drugs. 2022 Dec;40(6):1290-1297. doi: 10.1007/s10637-022-01303-w. Epub 2022 Sep 24.
Alpha-fetoprotein (AFP) response (relative decline in AFP) is associated with imaging response evaluated by response evaluation criteria in solid tumors ver1.1 (RECIST) and survival in treatment for hepatocellular carcinoma (HCC). However, the optimal threshold of AFP response is still unknown, especially in atezolizumab and bevacizumab (Atez/Bev) treatment. In this prospective multicenter study, we aimed to investigate an optimal threshold of AFP response in Atez/Bev treatment. Out of 284 patients with unresectable HCC who were treated with Atez/Bev, 91 patients with AFP ≥ 10 ng/ml were enrolled in the multicenter study. We investigated the relationship between various AFP response thresholds (relative decline ≥ 20%, ≥ 50%, and ≥ 75%) and treatment response and progression-free survival (PFS). An AFP relative decrease of ≥ 50% was associated with an overall response rate (ORR) with an odds ratio (95% confidence interval [CI]) of 5.7 (1.9-17). Disease control rate (DCR) was associated with an AFP relative decrease of ≥ 20%, with a 100% positive predictive value and a 52.0% sensitivity. AFP relative decreases of ≥ 50% and ≥ 20% were significantly associated with PFS with a hazard ratio (HR) of 5.60 (95% CI: 1.6-19, p = 0.006) and a HR of 4.44 (95% CI: 1.9-10, p < 0.001), respectively. AFP response of ≥ 50% and ≥ 20% were related to ORR and DCR, respectively, and both of these responses were also associated with PFS. AFP can be used as a real-time monitor during Atez/Bev treatment and is helpful for treatment optimization.
甲胎蛋白（AFP）应答（AFP 相对下降）与实体瘤反应评估标准 1.1（RECIST）评价的影像学应答和肝细胞癌（HCC）治疗的生存相关。然而，AFP 应答的最佳阈值仍不清楚，尤其是在阿替利珠单抗和贝伐珠单抗（Atez/Bev）治疗中。在这项前瞻性多中心研究中，我们旨在研究 Atez/Bev 治疗中 AFP 应答的最佳阈值。在接受 Atez/Bev 治疗的 284 例不可切除 HCC 患者中，纳入了 91 例 AFP≥10ng/ml 的患者进行多中心研究。我们研究了各种 AFP 应答阈值（相对下降≥20%、≥50%和≥75%）与治疗应答和无进展生存期（PFS）之间的关系。AFP 相对下降≥50%与总缓解率（ORR）相关，优势比（95%置信区间[CI]）为 5.7（1.9-17）。疾病控制率（DCR）与 AFP 相对下降≥20%相关，具有 100%的阳性预测值和 52.0%的敏感性。AFP 相对下降≥50%和≥20%与 PFS 显著相关，风险比（HR）分别为 5.60（95%CI：1.6-19，p=0.006）和 4.44（95%CI：1.9-10，p<0.001）。AFP 应答≥50%和≥20%分别与 ORR 和 DCR 相关，这两种应答均与 PFS 相关。AFP 可作为 Atez/Bev 治疗期间的实时监测指标，有助于优化治疗。
