Clinical Outcome and Treatment Sequences of Patients with Advanced Pancreatic Cancer Treated with Contemporary Chemotherapy Protocols.

IF 2 4区 医学 Q3 ONCOLOGY Oncology Research and Treatment Pub Date : 2023-01-01 Epub Date: 2023-01-31 DOI:10.1159/000529452
Julius Roehrle, Stefan Kasper, Jürgen-Walter Treckmann, Peter Markus, Brigitte Schumacher, David Albers, Johanna Wendling, Saskia Ting, Bastian Mende, Marlene Maßmann, Maximilian Markus, Isabel Virchow, Vivian Rosery, Katharina Laue, Gregor Zaun, Karina Kostbade, Michael Pogorzelski, Timm M Reissig, Sven-Thorsten Liffers, Kurt Schmid, Hans-Ulrich Schildhaus, Martin Schuler, Jens T Siveke, Marcel Wiesweg
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Abstract

Introduction: Systemic therapy is firmly established in patients with advanced or metastatic pancreatic ductal adenocarcinoma (PDAC). Clinical efficacy is still modest and options are limited. Combination therapy protocols such as FOLFIRINOX and gemcitabine/nab-paclitaxel (Gem/NP) define standard-of-care. Patients may receive a sequence of both regimens as first- and second-line palliative treatment. However, there is no guidance regarding a preferred order. Methods: This is a retrospective analysis of clinical characteristics, treatment trajectories, and outcomes of patients with advanced PDAC treated at the West German Cancer Center Essen from 2014 to 2020 to inform treatment decisions with respect to predictive factors, impact of chemotherapy regimen sequence, and maintenance treatment. Results: We identified 170 patients with available follow-up. Of those, 160 (94.1%) patients received palliative CTX for primary metastatic, locally advanced, or recurrent PDAC. Median progression-free survival (PFS) upon first palliative chemotherapy was 4.1 (3.1–5.9) months. First-line FOLFIRINOX was associated with superior PFS (median 6.3 months) and OS (9.7 months, HR 0.7, p = 0.03) as compared to Gem/NP or other regimens (PFS 3.0, OS 6.9 months). However, OS benefit of first-line FOLFIRINOX was lost in patients who received at least two treatment lines (median OS 12.1 vs. 13.1 months, p = 0.43). A landmark analysis of patients with clinical benefit (defined as CR/PR/SD for at least 20 weeks) upon first-line therapy revealed improved OS (HR 0.53, p = 0.02) for patients receiving continued deescalated maintenance therapy. Second-line regimens resulted in similar PFS (overall log-rank p = 0.92, median PFS upon second-line therapy 2.3 [1.8–2.9], per-regimen median between 1.8 and 3.9 months). A previously established systemic inflammation score proved to be strongly prognostic and allowed identification of a patient subgroup with dismal prognosis (OS 2.9 vs. 11.4 months, HR 5.23, p < 0.001), independent of other prognostic factors and with no relevant interaction with the choice of first-line regimen. Conclusion: In this real-world population of PDAC patients treated with contemporary combination chemotherapies, a positive impact of first-line FOLFIRINOX was only observed when no second or further line treatment was administered. Intensity-reduced maintenance therapy may lead to superior survival.
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采用当代化疗方案治疗晚期胰腺癌患者的临床效果和治疗顺序
简介:对于晚期或转移性胰腺导管腺癌(PDAC)患者,系统治疗已得到广泛认可。但临床疗效不佳,可选方案有限。FOLFIRINOX 和吉西他滨/纳布紫杉醇(Gem/NP)等联合治疗方案是标准疗法。作为一线和二线姑息治疗,患者可依次接受这两种治疗方案。然而,目前还没有关于首选顺序的指南:这是对2014年至2020年在埃森西德癌症中心接受治疗的晚期PDAC患者的临床特征、治疗轨迹和预后进行的回顾性分析,旨在就预测因素、化疗方案顺序的影响以及维持治疗等方面为治疗决策提供参考:结果:我们确定了170名有随访记录的患者。其中,160 例(94.1%)患者因原发性转移、局部晚期或复发性 PDAC 而接受了姑息性 CTX 治疗。首次姑息化疗的中位无进展生存期(PFS)为4.1(3.1-5.9)个月。与 Gem/NP 或其他方案(PFS 3.0,OS 6.9 个月)相比,一线 FOLFIRINOX 的 PFS(中位 6.3 个月)和 OS(9.7 个月,HR 0.7,P = 0.03)更优。然而,接受至少两个疗程治疗的患者失去了一线 FOLFIRINOX 的 OS 益处(中位 OS 12.1 个月 vs. 13.1 个月,p = 0.43)。对一线治疗后临床获益(定义为至少 20 周的 CR/PR/SD)的患者进行的里程碑式分析显示,继续接受降级维持治疗的患者的 OS 有所改善(HR 0.53,p = 0.02)。二线治疗方案的 PFS 相似(总体对数秩 p = 0.92,二线治疗的中位 PFS 为 2.3 [1.8-2.9],每个治疗方案的中位数为 1.8 至 3.9 个月)。事实证明,先前确定的全身炎症评分具有很强的预后作用,可以识别出预后不良的患者亚组(OS 2.9 vs. 11.4个月,HR 5.23,p <0.001),不受其他预后因素的影响,与一线治疗方案的选择也没有相关的相互作用:结论:在这批接受现代联合化疗的PDAC患者中,一线FOLFIRINOX只有在不进行二线或三线治疗时才会产生积极影响。减轻化疗强度的维持治疗可能会提高患者的生存率。
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来源期刊
CiteScore
3.20
自引率
0.00%
发文量
84
期刊介绍: With the first issue in 2014, the journal ''Onkologie'' has changed its title to ''Oncology Research and Treatment''. By this change, publisher and editor set the scene for the further development of this interdisciplinary journal. The English title makes it clear that the articles are published in English – a logical step for the journal, which is listed in all relevant international databases. For excellent manuscripts, a ''Fast Track'' was introduced: The review is carried out within 2 weeks; after acceptance the papers are published online within 14 days and immediately released as ''Editor’s Choice'' to provide the authors with maximum visibility of their results. Interesting case reports are published in the section ''Novel Insights from Clinical Practice'' which clearly highlights the scientific advances which the report presents.
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