Muhammad Ahsan Javed1, Georg Beyer2, Nha Le3, Alessio Vinci4, Helen Wong5, Daniel Palmer6, Robert D Morgan7, Angela Lamarca7, Richard A Hubner7, Juan W Valle8, Salma Alam9, Sumsur Chowdhury9, Yuk Ting Ma9, Livia Archibugi10, Gabriele Capurso10, Patrick Maisonneuve11, Albrecht Neesse12, Malin Sund13, Marvin Schober14, Sebastian Krug14. 1. NIHR Liverpool Pancreas Biomedical Research Unit, Institute of Translational Medicine, Royal Liverpool University Hospital, United Kingdom. 2. Department of Medicine A, University Medicine Greifswald, Greifswald, Germany; Medical Department II, University Hospital, LMU, Munich, Germany. 3. Gastroenterology Division, Second Internal Medicine Department, Semmelweis University, Budapest, Hungary. 4. University of Pavia, Department of Surgery, S. Matteo University Hospital Foundation, Pavia, Italy. 5. Department of Quality and Information Intelligence, The Clatterbridge Cancer Centre NHS Foundation Trust, Wirral, United Kingdom. 6. Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, United Kingdom. 7. Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, United Kingdom. 8. Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, United Kingdom; Institute of Cancer Sciences, University of Manchester, Manchester, United Kingdom. 9. Department of Hepatobiliary Oncology, New Queen Elizabeth Hospital Birmingham, Birmingham, United Kingdom. 10. Digestive and Liver Disease Unit, S. Andrea Hospital, University Sapienza, Rome, Italy. 11. Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan, Italy. 12. University Medical Centre Göttingen, Department of Gastroenterology and Gastrointestinal Oncology, Göttingen, Germany. 13. University of Umea, Department of Surgical and Perioperative Sciences, Umea, Sweden. Electronic address: malin.sund@surgery.umu.se. 14. Department of Gastroenterology and Hepatology, Martin-Luther-University Halle-Wittenberg, Halle, Germany.
Abstract
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is associated with poor prognosis. Gemcitabine is the standard chemotherapy for patients with metastatic pancreatic adenocarcinoma (MPA). Randomized clinical trials evaluating intensified chemotherapies including FOLFIRINOX and nab-paclitaxel plus gemcitabine (NAB+GEM) have shown improvement in survival. Here, we have evaluated the efficacy of intensified chemotherapy versus gemcitabine monotherapy in real-life settings across Europe. METHODS: A retrospective multi-center study including 1056 MPA patients, between 2012 and 2015, from nine centers in UK, Germany, Italy, Hungary and the Swedish registry was performed. Follow-up was at least 12 months. Cox proportional Harzards regression was used for uni- and multivariable evaluation of prognostic factors. RESULTS: Of 1056 MPA patients, 1030 (98.7%) were assessable for survival analysis. Gemcitabine monotherapy was the most commonly used regimen (41.3%), compared to FOLFIRINOX (n = 204, 19.3%), NAB+GEM (n = 81, 7.7%) and other gemcitabine- or 5-FU-based regimens (n = 335, 31.7%). The median overall survival (OS) was: FOLFIRINOX 9.9 months (95%CI 8.4-12.6), NAB+GEM 7.9 months (95%CI 6.2-10.0), other combinations 8.5 months (95%CI 7.7-9.3) and gemcitabine monotherapy 4.9 months (95%CI 4.4-5.6). Compared to gemcitabine monotherapy, any combination of chemotherapeutics improved the survival with no significant difference between the intensified regimens. Multivariable analysis showed an association between treatment center, male gender, inoperability at diagnosis and performance status (ECOG 1-3) with poor prognosis. CONCLUSION: Gemcitabine monotherapy was predominantly used in 2012-2015. Intensified chemotherapy improved OS in comparison to gemcitabine monotherapy. In real-life settings, the OS rates of different treatment approaches are lower than shown in randomized phase III trials.
BACKGROUND:Pancreatic ductal adenocarcinoma (PDAC) is associated with poor prognosis. Gemcitabine is the standard chemotherapy for patients with metastatic pancreatic adenocarcinoma (MPA). Randomized clinical trials evaluating intensified chemotherapies including FOLFIRINOX and nab-paclitaxel plus gemcitabine (NAB+GEM) have shown improvement in survival. Here, we have evaluated the efficacy of intensified chemotherapy versus gemcitabine monotherapy in real-life settings across Europe. METHODS: A retrospective multi-center study including 1056 MPA patients, between 2012 and 2015, from nine centers in UK, Germany, Italy, Hungary and the Swedish registry was performed. Follow-up was at least 12 months. Cox proportional Harzards regression was used for uni- and multivariable evaluation of prognostic factors. RESULTS: Of 1056 MPA patients, 1030 (98.7%) were assessable for survival analysis. Gemcitabine monotherapy was the most commonly used regimen (41.3%), compared to FOLFIRINOX (n = 204, 19.3%), NAB+GEM (n = 81, 7.7%) and other gemcitabine- or 5-FU-based regimens (n = 335, 31.7%). The median overall survival (OS) was: FOLFIRINOX 9.9 months (95%CI 8.4-12.6), NAB+GEM 7.9 months (95%CI 6.2-10.0), other combinations 8.5 months (95%CI 7.7-9.3) and gemcitabine monotherapy 4.9 months (95%CI 4.4-5.6). Compared to gemcitabine monotherapy, any combination of chemotherapeutics improved the survival with no significant difference between the intensified regimens. Multivariable analysis showed an association between treatment center, male gender, inoperability at diagnosis and performance status (ECOG 1-3) with poor prognosis. CONCLUSION:Gemcitabine monotherapy was predominantly used in 2012-2015. Intensified chemotherapy improved OS in comparison to gemcitabine monotherapy. In real-life settings, the OS rates of different treatment approaches are lower than shown in randomized phase III trials.
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