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      Folfirinox versus gemcitabine/nab-paclitaxel as first-line therapy in patients with metastatic pancreatic cancer: a comparative propensity score study

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          Abstract

          Background:

          Folfirinox (FFX) and gemcitabine/nab-paclitaxel (GN) are both standard first-line treatments in patients with metastatic pancreatic cancer (mPC). However, data comparing these two chemotherapeutic regimens and their sequential use remain scarce.

          Methods:

          Data from two independent cohorts enrolling patients treated with FFX ( n = 107) or GN ( n = 109) were retrospectively pooled. Primary endpoint was overall survival (OS). Progression-free survival (PFS) was the secondary endpoint. A propensity score based on age, gender, performance status (PS), and presence of liver metastases was used to make groups comparable.

          Results:

          In the whole study population, OS was significantly higher in FFX (14 months; 95% CI: 10–21) than in GN groups (9 months; 95% CI: 8–12) before ( p = 0.008) and after ( p = 0.021) adjusting for age, number of metastatic sites, liver metastases, peritoneal carcinomatosis and CA19.9 level at baseline. PFS tends to be higher in FFX (6 months) than GN groups (5 months; p = 0.053). After matching ( n = 49/group), patients were comparable for all baseline characteristics including PS. In the matched population, there was a trend toward greater OS in patients treated with FFX (HR = 0.67; p = 0.097). However, survival in each group was not solely a result of the first-line regimen. The proportion of patients who were fit for GN after FFX failure (FFX–GN sequence) was higher (46.9%) than the reverse sequence (20.4%; p = 0.01), which suggests a higher feasibility for the FFX–GN sequence. Corresponding median OS were 19 months versus 9.5 months, respectively ( p = 0.094).

          Conclusion:

          This study shows greater OS with FFX than with GN in patients with mPC. GN after FFX failure appears more feasible than the reverse sequence.

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          Most cited references17

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          MatchIt: Nonparametric Preprocessing for Parametric Causal Inference

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            Consensus report of the national cancer institute clinical trials planning meeting on pancreas cancer treatment.

            Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer mortality, despite significant improvements in diagnostic imaging and operative mortality rates. The 5-year survival rate remains less than 5% because of microscopic or gross metastatic disease at time of diagnosis. The Clinical Trials Planning Meeting in pancreatic cancer was convened by the National Cancer Institute's Gastrointestinal Cancer Steering Committee to discuss the integration of basic and clinical knowledge in the design of clinical trials in PDAC. Major emphasis was placed on the enhancement of research to identify and validate the relevant targets and molecular pathways in PDAC, cancer stem cells, and the microenvironment. Emphasis was also placed on developing rational combinations of targeted agents and the development of predictive biomarkers to assist selection of patient subsets. The development of preclinical tumor models that are better predictive of human PDAC must be supported with wider availability to the research community. Phase III clinical trials should be implemented only if there is a meaningful clinical signal of efficacy and safety in the phase II setting. The emphasis must therefore be on performing well-designed phase II studies with uniform sets of basic entry and evaluation criteria with survival as a primary endpoint. Patients with either metastatic or locally advanced PDAC must be studied separately.
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              Nab-paclitaxel plus gemcitabine for metastatic pancreatic adenocarcinoma after Folfirinox failure: an AGEO prospective multicentre cohort

              Background: There is currently no standard second-line treatment for metastatic pancreatic adenocarcinoma (MPA), and progression-free survival is consistently <4 months in this setting. The aim of this study was to evaluate the efficacy and tolerability of Nab-paclitaxel plus gemcitabine (A+G) after Folfirinox failure in MPA. Methods: From February 2013 to July 2014, all consecutive patients treated with A+G for histologically proven MPA after Folfirinox failure were prospectively enrolled in 12 French centres. A+G was delivered as described in the MPACT trial, until disease progression, patient refusal or unacceptable toxicity. Results: Fifty-seven patients were treated with Nab-paclitaxel plus gemcitabine, for a median of 4 cycles (range 1–12). The disease control rate was 58%, with a 17.5% objective response rate. Median overall survival (OS) was 8.8 months (95% CI: 6.2–9.7) and median progression-free survival was 5.1 months (95% CI: 3.2–6.2). Since the start of first-line chemotherapy, median OS was 18 months (95% CI: 16–21). No toxic deaths occurred. Grade 3–4 toxicities were reported in 40% of patients, consisting of neutropenia (12.5%), neurotoxicity (12.5%), asthenia (9%) and thrombocytopenia (6.5%). Conclusions: A+G seems to be effective, with a manageable toxicity profile, after Folfirinox failure in patients with MPA.
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                Author and article information

                Contributors
                Journal
                Therap Adv Gastroenterol
                Therap Adv Gastroenterol
                TAG
                sptag
                Therapeutic Advances in Gastroenterology
                SAGE Publications (Sage UK: London, England )
                1756-283X
                1756-2848
                25 September 2019
                2019
                : 12
                : 1756284819878660
                Affiliations
                [1-1756284819878660]Hepatogastroenterology Department, University Hospital of Saint-Etienne, Avenue Albert Raimond, Saint-Etienne 42270, France
                [2-1756284819878660]EA 7425 HESPER, Health Services and Performance Research, Claude Bernard Lyon 1 University, Lyon, France
                [3-1756284819878660]Department of Medical Oncology, Antoine Lacassagne Center, Nice, France
                [4-1756284819878660]Department of Gastroenterology and Gastro-intestinal Oncology, Hôpital Européen Georges-Pompidou, APHP, Paris Descartes University, Sorbonne Paris Cité, Paris, France
                [5-1756284819878660]Department of Gastroenterology, Poitiers University Hospital, Poitiers, France
                [6-1756284819878660]Department of GI Oncology, Hôpital Européen Georges-Pompidou, APHP, Paris Descartes University, Sorbonne Paris Cité, Paris, France
                [7-1756284819878660]Methodology and Quality of Life in Oncology Unit (INSERM UMR 1098), University Hospital of Besançon, Besançon, France
                [8-1756284819878660]Department of Medical oncology, Bergonié Institut, Bordeaux, France
                [9-1756284819878660]Department of Medical Oncology, Saint-Antoine Hospital, Paris, France
                [10-1756284819878660]Gastroenterology Unit, Saint-Louis Teaching Hospital, Paris, France
                [11-1756284819878660]Department of Gastroenterology, Amiens-Picardie University Hospital, Amiens, France
                [12-1756284819878660]Department of Gastroenterology, CH Meaux, Meaux, France
                [13-1756284819878660]Department of Oncology, Hôpital Privé Jean Mermoz, Lyon, France
                [14-1756284819878660]Department of Oncology, Hôpital Privé Jean Mermoz, Lyon, France
                [15-1756284819878660]Department of Gastroenterology, Hôpital Kremlin Bicêtre, Le Kremlin-Bicêtre, Paris, France
                [16-1756284819878660]Department of Digestive and Hepatobiliary Surgery, University Hospital of Saint-Etienne, Saint-Priest-en-Jarez, France
                [17-1756284819878660]Department of Digestive and Hepatobiliary Surgery, University Hospital of Clermont-Ferrand, Clermont-Ferrand, France
                [18-1756284819878660]Department of Hepatogastroenterology, University Hospital of Saint-Etienne, Saint-Etienne, France
                [19-1756284819878660]EA 7425 HESPER, Health Services and Performance Research, Claude Bernard Lyon 1 University, Lyon, France
                [20-1756284819878660]Department of Gastroenterology and Gastro-intestinal Oncology, Hôpital Européen Georges-Pompidou, APHP, Paris Descartes University, Sorbonne Paris Cité, Paris, France
                Author notes
                Author information
                https://orcid.org/0000-0002-7296-5464
                Article
                10.1177_1756284819878660
                10.1177/1756284819878660
                6764033
                31598136
                ec3726cf-5869-4ffb-8e63-6fd004106c51
                © The Author(s), 2019

                This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                : 3 May 2019
                : 16 August 2019
                Categories
                Study Protocol
                Custom metadata
                January-December 2019

                folfirinox,gemcitabine/nab-paclitaxel,metastatic,pancreatic adenocarcinoma,survival

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