多药诱导化疗治疗局部晚期胰腺癌中 CA19-9 的预后和预测价值：一项前瞻性、多中心 II 期试验（NEOLAP-AIO-PAK-0113）的结果。
Prognostic and predictive value of CA 19-9 in locally advanced pancreatic cancer treated with multiagent induction chemotherapy: results from a prospective, multicenter phase II trial (NEOLAP-AIO-PAK-0113).
机构信息
Department of Internal Medicine II, Medical Oncology and Comprehensive Cancer Center Mainfranken, University Hospital Würzburg, Würzburg, Germany.
Department of Medical Oncology, Bridge Institute of Experimental Tumor Therapy, University Medicine Essen, Essen, Germany; Division of Solid Tumor Translational Oncology (DKTK Partner Site Essen, DKFZ Heidelberg), West German Cancer Center, University Medicine Essen, Essen, Germany.
出版信息
ESMO Open. 2022 Aug;7(4):100552. doi: 10.1016/j.esmoop.2022.100552. Epub 2022 Aug 12.
BACKGROUND
The prognostic and predictive value of carbohydrate antigen 19-9 (CA 19-9) in locally advanced pancreatic cancer (LAPC) has not yet been defined from prospective randomized controlled trials (RCTs).
PATIENTS AND METHODS
A total of 165 LAPC patients were treated within the NEOLAP RCT for 16 weeks with multiagent induction chemotherapy [ICT; either nab-paclitaxel/gemcitabine alone or nab-paclitaxel/gemcitabine followed by FOLFIRINOX (combination of fluorouracil, leucovorin, irinotecan, and oxaliplatin)] followed by surgical exploration of all patients without evidence of disease progression. CA 19-9 was determined at baseline and after ICT and correlated with overall survival (OS) and secondary R0 resection rate.
RESULTS
From the NEOLAP study population (N = 165) 133 patients (81%) were evaluable for CA 19-9 at baseline and 81/88 patients (92%) for post-ICT CA 19-9 response. Median OS (mOS) in the CA 19-9 cohort (n = 133) was 16.2 months [95% confidence interval (CI) 13.0-19.4] and R0 resection (n = 31; 23%) was associated with a significant survival benefit [40.8 months (95% CI 21.7-59.8)], while R1 resected patients (n = 14; 11%) had no survival benefit [14.0 (95% CI 11.7-16.3) months, hazard ratio (HR) 0.27; P = 0.001]. After ICT most patients showed a CA 19-9 response (median change from baseline: -82%; relative decrease ≥55%: 83%; absolute decrease to ≤50 U/ml: 43%). Robust CA 19-9 response (decrease to ≤50U/ml) was significantly associated with mOS [27.8 (95% CI 18.4-37.2) versus 16.5 (95% CI 11.7-21.2) months, HR 0.49; P = 0.013], whereas CA 19-9 baseline levels were not prognostic for OS. Multivariate analysis demonstrated that a robust CA 19-9 response was an independent predictive factor for R0 resection. Using a CA 19-9 decrease to ≤61 U/ml as optimal cut-off (by receiver operating characteristic analysis) yielded 72% sensitivity and 62% specificity for successful R0 resection, whereas CA 19-9 nonresponders (<20% decrease or increase) had no chance for successful R0 resection.
CONCLUSIONS
CA 19-9 response after multiagent ICT provides relevant prognostic and predictive information and is useful in selecting LAPC patients for explorative surgery.
CLINICAL TRIAL NUMBER
ClinicalTrials.govNCT02125136; https://clinicaltrials.gov/ct2/show/NCT02125136; EudraCT 2013-004796-12; https://www.clinicaltrialsregister.eu/ctr-search/trial/2013-004796-12/results.
背景
在局部晚期胰腺癌（LAPC）中，糖链抗原 19-9（CA 19-9）的预后和预测价值尚未从前瞻性随机对照试验（RCT）中得到明确界定。
患者和方法
共有 165 例 LAPC 患者在 NEOLAP RCT 中接受了 16 周的多药诱导化疗[ICT；单独使用nab-紫杉醇/吉西他滨或 nab-紫杉醇/吉西他滨后 FOLFIRINOX（氟尿嘧啶、亚叶酸、伊立替康和奥沙利铂的联合）]，随后所有患者均进行了无疾病进展的手术探查。在基线和 ICT 后测定 CA 19-9，并将其与总生存期（OS）和继发性 R0 切除率相关联。
结果
从 NEOLAP 研究人群（N=165）中，有 133 例患者（81%）可评估基线 CA 19-9，81/88 例患者（92%）可评估 ICT 后 CA 19-9 反应。在 CA 19-9 队列（n=133）中，中位 OS（mOS）为 16.2 个月[95%置信区间（CI）13.0-19.4]，R0 切除（n=31；23%）与显著的生存获益相关[40.8 个月（95%CI 21.7-59.8)]，而 R1 切除患者（n=14；11%）则没有生存获益[14.0（95%CI 11.7-16.3）个月，风险比（HR）0.27；P=0.001]。在 ICT 后，大多数患者表现出 CA 19-9 反应（中位数与基线相比下降：-82%；相对下降≥55%：83%；绝对下降至≤50 U/ml：43%）。强有力的 CA 19-9 反应（下降至≤50U/ml）与 mOS 显著相关[27.8（95%CI 18.4-37.2）与 16.5（95%CI 11.7-21.2）个月，HR 0.49；P=0.013]，而 CA 19-9 基线水平与 OS 无关。多变量分析表明，强有力的 CA 19-9 反应是 R0 切除的独立预测因素。使用 CA 19-9 下降至≤61 U/ml 作为最佳截断值（通过接受者操作特征分析），对于成功的 R0 切除，敏感性为 72%，特异性为 62%，而 CA 19-9 无反应者（<20%下降或增加）则没有成功进行 R0 切除的机会。
结论
多药 ICT 后 CA 19-9 反应提供了相关的预后和预测信息，并有助于选择适合手术探查的 LAPC 患者。
临床试验编号
ClinicalTrials.govNCT02125136；https://clinicaltrials.gov/ct2/show/NCT02125136；EudraCT 2013-004796-12；https://www.clinicaltrialsregister.eu/ctr-search/trial/2013-004796-12/results。
Zotero 插件