转移性胰腺导管腺癌患者分子定制治疗的试点试验。

Journal of Pancreatic Cancer Pub Date : 2019-05-02 eCollection Date: 2019-01-01 DOI:10.1089/pancan.2019.0003
Anteneh A Tesfaye, Hongkun Wang, Marion L Hartley, Aiwu Ruth He, Louis Weiner, Nina Gabelia, Lana Kapanadze, Muhammad Shezad, Jonathan R Brody, John L Marshall, Michael J Pishvaian
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引用次数: 2

摘要

目的:尽管肿瘤分子谱被广泛采用,但缺乏证据表明,用于转移性胰腺癌患者治疗选择的分子生物标志物与预测治疗结果之间存在联系。我们启动了一项试点研究,以测试设计转移性胰腺癌分子定制治疗的更大规模II期试验的可行性。方法:我们的研究旨在评估基于三种已发表的化疗反应预测标志物表达的治疗算法的可行性:核糖核苷酸还原酶催化亚基M1(用于吉西他滨);切除修复交叉互补组1(用于铂类药物);在未经治疗的转移性胰腺癌患者中胸苷酸合成酶(用于5-氟尿嘧啶)。肿瘤活检分析的结果用于将患者分配到七个双重方案中的一个。主要次要目标包括缓解率(RR)、疾病控制率(DCR)、无进展生存期(PFS)和总生存期(OS)。结果:2012年12月至2015年3月,30例患者入组研究。10例患者未通过筛查,主要原因是肿瘤组织可用性不足。在剩余的20名患者中,19名患者被分配到6个不同的化疗双药组,RR为28%,DCR率为78%。中位PFS和OS分别为5.78和8.21个月。结论:将生物标志物纳入治疗算法是可行的,并导致转移性胰腺癌患者的PFS和OS类似于其他双重治疗。基于该试点研究的结果,一项更大规模的II期随机试验已经在二线环境(NCT02967770)启动了分子靶向治疗与医生选择的标准治疗。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

A Pilot Trial of Molecularly Tailored Therapy for Patients with Metastatic Pancreatic Ductal Adenocarcinoma.

A Pilot Trial of Molecularly Tailored Therapy for Patients with Metastatic Pancreatic Ductal Adenocarcinoma.

A Pilot Trial of Molecularly Tailored Therapy for Patients with Metastatic Pancreatic Ductal Adenocarcinoma.

A Pilot Trial of Molecularly Tailored Therapy for Patients with Metastatic Pancreatic Ductal Adenocarcinoma.

Purpose: Despite the wide adoption of tumor molecular profiling, there is a dearth of evidence linking molecular biomarkers for treatment selection to prediction of treatment outcomes in patients with metastatic pancreatic cancer. We initiated a pilot study to test the feasibility of designing a larger phase II trial of molecularly tailored treatment for metastatic pancreatic cancer. Methods: Our study aimed to assess the feasibility of following a treatment algorithm based on the expression of three published predictive markers of response to chemotherapy: ribonucleotide reductase catalytic subunit M1 (for gemcitabine); excision repair cross-complementation group 1 (for platinum agents); and thymidylate synthase (for 5-fluorouracil) in patients with untreated, metastatic pancreatic cancer. Results of the tumor biopsy analysis were used to assign patients to one of seven doublet regimens. Key secondary objectives included response rate (RR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Results: Between December 2012 and March 2015, 30 patients were enrolled into the study. Ten patients failed screening primarily due to inadequate tumor tissue availability. Of the remaining 20 patients, 19 were assigned into 6 different chemotherapy doublets, and achieved an RR of 28%, with a DCR rate of 78%. The median PFS and OS were 5.78 and 8.21 months, respectively. Conclusions: The incorporation of biomarkers into a treatment algorithm is feasible and resulted in a PFS and OS similar to other doublet therapies for patients with metastatic pancreatic cancer. Based on the results from this pilot study, a larger phase II randomized trial of molecularly targeted therapy versus physicians' choice of standard of care has been initiated in the second-line setting (NCT02967770).

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