학술논문
Gemcitabine plus nab-paclitaxel until progression or alternating with FOLFIRI.3, as first-line treatment for patients with metastatic pancreatic adenocarcinoma: The Federation Francophone de Cancérologie Digestive-PRODIGE 37 randomised phase II study (FIRGEMAX).
Document Type
Academic Journal
Author
Rinaldi Y; Department of Hepato-gastroenterology, European Hospital, Marseille, France.; Pointet AL; Department of Hepato-gastroenterology, Georges Pompidou European Hospital, Paris, France.; Khemissa Akouz F; Department of Hepato-gastroenterology, Saint Jean Hospital, Perpignan, France.; Le Malicot K; Biostatistics Department, Francophone Federation of Digestive Cancerology, EPICAD INSERM LNC-UMR 1231, University of Burgundy and Franche Comté, Dijon, France.; Wahiba B; Department of Hepato-gastroenterology, European Hospital, Marseille, France.; Louafi S; Department of Oncology, Sud Francilien Hospital Center, Corbeil-Essonnes, France.; Gratet A; Oncology and Hematology ONCOSUD Unit, Clinic Pasteur, Toulouse, France.; Miglianico L; Department of Radiotherapy, Private Hospital Center, Saint-Grégoire, France.; Laharie H; Department of Oncology and Radiotherapy, Clinic Tivoli, Bordeaux, France.; Bouhier Leporrier K; Department of Hepato-gastroenterology, University Hospital, Caen, France.; Thirot Bidault A; Department of Hepato-gastroenterology, Private Hospital, Antony, France.; Texereau P; Department of Hepato-gastroenterology, Layne Hospital, Mont-De-Marsan, France.; Coriat R; Department of Hepato-gastroenterology, Cochin Hospital, APHP, Paris, France.; Terrebonne E; Department of Hepato-gastroenterology, Haut Lévêque Hospital, Pessac, France.; Gouttebel MC; Department of Oncology, Drôme Nord Hospital, Romans Sur Isère, France.; Malka D; Department of Hepato-gastroenterology, Gustave Roussy Cancer Campus, Villejuif, France.; Bachet JB; Department of Hepato-gastroenterology, Pitié-Salpêtrière Hospital, Paris, France.; Lepage C; Department of Hepato-gastroenterology, University Hospital of Dijon, EPICAD INSERM LNC-UMR 1231, University of Burgundy and Franche Comté, Dijon, France.; Taieb J; Department of Hepato-gastroenterology, Sorbonne Paris City, Paris Descartes University, Georges Pompidou European Hospital, Paris, France. Electronic address: jtaieb75@gmail.com.
Source
Publisher: Elsevier Science Ltd Country of Publication: England NLM ID: 9005373 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0852 (Electronic) Linking ISSN: 09598049 NLM ISO Abbreviation: Eur J Cancer Subsets: MEDLINE
Subject
Language
English
Abstract
Background: Chemotherapy is effective in metastatic pancreatic adenocarcinoma (mPA), but new approaches are still needed to improve patients' survival and quality of life. We have previously published good efficacy and tolerability results on a sequential treatment strategy of gemcitabine followed by an intensified FOLFIRI (5FU+irinotecan) regimen. In the present study, we evaluated the same sequence but replaced gemcitabine by the new gemcitabine + nab-paclitaxel standard first-line combination.
Patients and Methods: We randomised chemotherapy-naive patients with proven mPA, bilirubin levels ≤1.5 upper limit of normal values and performance status 0-2 to alternately receive gemcitabine + nab-paclitaxel for 2 months then FOLFIRI.3 for 2 months in arm A, or gemcitabine + nab-paclitaxel alone until progression in arm B. The primary objective was to increase the 6-month progression-free survival (PFS) rate from 40% (H0 ) to 60% (H 1 ); using the binomial exact method, 124 patients were required. Analyses were carried out in preplanned modified intention-to-treat (mITT) and per-protocol (PP) populations.
Results: Between November 2015 and November 2016, 127 patients were enrolled. Main grade III-IV toxicities (% in arm A/B) were: diarrhoea (12.5/1.7), neutropenia (46.9/31, including febrile neutropenia: 1.6/0), skin toxicity (6.3/13.8), and peripheral neuropathy (6.3/8.6). No toxic deaths occurred. The objective response rate was 40.3% (95% confidence interval [CI]: 28.1-53.6) in arm A and 26.7% (95% CI: 16.1-39.7) in arm B. The primary end-point (6-month PFS rate) was 45.2% [one-sided 95% CI: 34.3-56.4] in arm A and 23.3% in arm B [one-sided 95% CI: 14.3-32.3] in the mITT population. In the PP population, median PFS and OS were 7.6 months and 6 months and 14.5 months and 12.2 months in arm A and B, respectively.
Conclusions: The FIRGEMAX strategy with gemcitabine + nab-paclitaxel alternating with FOLFIRI.3 every 2 months, appears feasible and effective, with manageable toxicities, in patients able to reach >2mo of treatment.
Trial Registration Information: EudraCT: 2014-004449-28: NCT: 0282701.
Competing Interests: Conflict of interest statement T.J. reported receiving honoraria from Merck, Roche, Amgen, Lilly, Sanofi, Samsung, MSD, Servier, Celgene, Pierre Fabre; has been a member of the consulting or advisory role for Roche, Merck KGaA, Amgen, Lilly, MSD, Servier, Pierre Fabre, Sanofi, Samsung; speakers' Bureau for Servier, Amgen, Roche, Sanofi, Merck, Lilly, Pierre Fabre. R.Y. reported receiving honoraria from Roche, Sanofi, Merck, Amgen, Bayer and Servier. B.J-.B reported receiving honoraria from Amgen, AstraZeneca, Bayer, Merck Serono, Pierre Fabre, Roche, Sanofi, Servier. All the remaining authors have declared no conflicts of interest.
(Copyright © 2020 Elsevier Ltd. All rights reserved.)
Patients and Methods: We randomised chemotherapy-naive patients with proven mPA, bilirubin levels ≤1.5 upper limit of normal values and performance status 0-2 to alternately receive gemcitabine + nab-paclitaxel for 2 months then FOLFIRI.3 for 2 months in arm A, or gemcitabine + nab-paclitaxel alone until progression in arm B. The primary objective was to increase the 6-month progression-free survival (PFS) rate from 40% (H
Results: Between November 2015 and November 2016, 127 patients were enrolled. Main grade III-IV toxicities (% in arm A/B) were: diarrhoea (12.5/1.7), neutropenia (46.9/31, including febrile neutropenia: 1.6/0), skin toxicity (6.3/13.8), and peripheral neuropathy (6.3/8.6). No toxic deaths occurred. The objective response rate was 40.3% (95% confidence interval [CI]: 28.1-53.6) in arm A and 26.7% (95% CI: 16.1-39.7) in arm B. The primary end-point (6-month PFS rate) was 45.2% [one-sided 95% CI: 34.3-56.4] in arm A and 23.3% in arm B [one-sided 95% CI: 14.3-32.3] in the mITT population. In the PP population, median PFS and OS were 7.6 months and 6 months and 14.5 months and 12.2 months in arm A and B, respectively.
Conclusions: The FIRGEMAX strategy with gemcitabine + nab-paclitaxel alternating with FOLFIRI.3 every 2 months, appears feasible and effective, with manageable toxicities, in patients able to reach >2mo of treatment.
Trial Registration Information: EudraCT: 2014-004449-28: NCT: 0282701.
Competing Interests: Conflict of interest statement T.J. reported receiving honoraria from Merck, Roche, Amgen, Lilly, Sanofi, Samsung, MSD, Servier, Celgene, Pierre Fabre; has been a member of the consulting or advisory role for Roche, Merck KGaA, Amgen, Lilly, MSD, Servier, Pierre Fabre, Sanofi, Samsung; speakers' Bureau for Servier, Amgen, Roche, Sanofi, Merck, Lilly, Pierre Fabre. R.Y. reported receiving honoraria from Roche, Sanofi, Merck, Amgen, Bayer and Servier. B.J-.B reported receiving honoraria from Amgen, AstraZeneca, Bayer, Merck Serono, Pierre Fabre, Roche, Sanofi, Servier. All the remaining authors have declared no conflicts of interest.
(Copyright © 2020 Elsevier Ltd. All rights reserved.)