Massachusetts General Hospital Cancer Center, Boston, MA, USA.
Jiahui International Cancer Center, Jiahui Health, Shanghai, China.
Br J Cancer. 2021 Apr;124(8):1388-1397. doi: 10.1038/s41416-021-01260-w. Epub 2021 Feb 3.
Post hoc analyses assessed the prognostic and predictive value of baseline alpha-fetoprotein (AFP), as well as clinical outcomes by AFP response or progression, during treatment in two placebo-controlled trials (REACH, REACH-2).
Serum AFP was measured at baseline and every three cycles. The prognostic and predictive value of baseline AFP was assessed by Cox regression models and Subpopulation Treatment Effect Pattern Plot method. Associations between AFP (≥ 20% increase) and radiographic progression and efficacy were assessed.
Baseline AFP was confirmed as a continuous (REACH, REACH-2; p < 0.0001) and dichotomous (≥400 vs. <400 ng/ml; REACH, p < 0.01) prognostic factor, and was predictive for ramucirumab survival benefit in REACH (p = 0.0042 continuous; p < 0.0001 dichotomous). Time to AFP (hazard ratio [HR] 0.513; p < 0.0001) and radiographic (HR 0.549; p < 0.0001) progression favoured ramucirumab. Association between AFP and radiographic progression was shown for up to 6 (odds ratio [OR] 5.1; p < 0.0001) and 6-12 weeks (OR 1.8; p = 0.0065). AFP response was higher with ramucirumab vs. placebo (p < 0.0001). Survival was longer in patients with an AFP response than patients without (13.6 vs. 5.6 months, HR 0.451; 95% confidence interval, 0.354-0.574; p < 0.0001).
AFP is an important prognostic factor and a predictive biomarker for ramucirumab survival benefit. AFP ≥ 400 ng/ml is an appropriate selection criterion for ramucirumab.
ClinicalTrials.gov, REACH (NCT01140347) and REACH-2 (NCT02435433).
在两项安慰剂对照试验（REACH、REACH-2）中，事后分析评估了基线甲胎蛋白（AFP）以及治疗期间 AFP 反应或进展的临床结局的预后和预测价值。
在基线和每三个周期测量血清 AFP。使用 Cox 回归模型和亚组治疗效果模式图方法评估基线 AFP 的预后和预测价值。评估 AFP（≥20%增加）与放射学进展和疗效之间的关系。
基线 AFP 被确认为连续（REACH、REACH-2；p<0.0001）和二分类（≥400 与<400ng/ml；REACH，p<0.01）预后因素，并且对 REACH 中 ramucirumab 的生存获益具有预测价值（p=0.0042 连续；p<0.0001 二分类）。AFP 时间（风险比 [HR] 0.513；p<0.0001）和放射学进展（HR 0.549；p<0.0001）有利于 ramucirumab。在长达 6 周（优势比 [OR] 5.1；p<0.0001）和 6-12 周（OR 1.8；p=0.0065）时间内，均显示 AFP 与放射学进展之间存在关联。与安慰剂相比，ramucirumab 的 AFP 反应更高（p<0.0001）。有 AFP 反应的患者的生存时间长于没有 AFP 反应的患者（13.6 与 5.6 个月，HR 0.451；95%置信区间，0.354-0.574；p<0.0001）。
AFP 是 ramucirumab 生存获益的重要预后因素和预测生物标志物。AFP≥400ng/ml 是选择 ramucirumab 的合适标准。
ClinicalTrials.gov，REACH（NCT01140347）和 REACH-2（NCT02435433）。
