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
{"title":"Clinical Outcome and Treatment Sequences of Patients with Advanced Pancreatic Cancer Treated with Contemporary Chemotherapy Protocols.","authors":"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","doi":"10.1159/000529452","DOIUrl":null,"url":null,"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.","PeriodicalId":19543,"journal":{"name":"Oncology Research and Treatment","volume":"46 4","pages":"140-150"},"PeriodicalIF":2.0000,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Oncology Research and Treatment","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1159/000529452","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/1/31 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
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.
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.