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)

Yves Rinaldi; Anne Laure Pointet; Faiza Khemissa Akouz; Karine Le Malicot; Bidaut Wahiba; Samy Louafi; Alain Gratet; Laurent Miglianico; Hortense Laharie; Karine Bouhier Leporrier; Anne Thirot Bidault; Patrick Texereau; Romain Coriat; Eric Terrebonne; Marie Claude Gouttebel; David Malka; Jean Baptiste Bachet; Côme Lepage; Julien Taieb; Cécile Julien; Nicolas Barriere; Julie Gigout; Simon Pernot; Céline Lepere; Aziz Zaanan; Géraldine Perkins; Raymond Despax; Jérôme Chamois; Xavier Artignan; Pauline Regnault; Benoît Dupont; Maxime Lesouef; Leila Bengrine Lefevre; Julie Vincent; François Ghiringhelli; Mme E. Barbier; Morgan Andre; Johann Dreanic; Catherine Brezault-Bonnet; Valérie Boige; Antoine Holllebecque; Bruno Valenza; Gildas Phelip; Philippe Dominici; Marion Chauvenet; Frederick Moryoussef; Pierre Luc Etienne; Dominique Besson; Mathilde Martinez; Pamela Biondiani; Benoît Avisse; Marie Pierre Galais; Aurélie Parzy; Salvatore Caruso; Jean François Codoul; Iulia Pripon; Mustapha Atlassi; Oana Cojocarasu; Etienne Suc; Ahmed Bedjaoui; Philippe Houyau; Yann Berge; Dany Gargot; Vincent Bourgeois; Pierre Emmanuel Henneresse; Sandrine Lavau denes; Valérie Lebrun Lyat; Dominique Genet; Jean Martin; Pr Pierre Michel; David Sefrioui; Anne Escande; Louis Marie Dourthe

doi:10.1016/j.ejca.2020.05.018

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)

Yves Rinaldi, Anne Laure Pointet, Faiza Khemissa Akouz, Karine Le Malicot, Bidaut Wahiba, Samy Louafi, Alain Gratet, Laurent Miglianico, Hortense Laharie, Karine Bouhier Leporrier, Anne Thirot Bidault, Patrick Texereau, Romain Coriat, Eric Terrebonne, Marie Claude Gouttebel, David Malka, Jean Baptiste Bachet, Côme Lepage, Julien Taieb, Cécile JulienNicolas Barriere, Julie Gigout, Simon Pernot, Céline Lepere, Aziz Zaanan, Géraldine Perkins, Raymond Despax, Jérôme Chamois, Xavier Artignan, Pauline Regnault, Benoît Dupont, Maxime Lesouef, Leila Bengrine Lefevre, Julie Vincent, François Ghiringhelli, Mme E. Barbier, Morgan Andre, Johann Dreanic, Catherine Brezault-Bonnet, Valérie Boige, Antoine Holllebecque, Bruno Valenza, Gildas Phelip, Philippe Dominici, Marion Chauvenet, Frederick Moryoussef, Pierre Luc Etienne, Dominique Besson, Mathilde Martinez, Pamela Biondiani, Benoît Avisse, Marie Pierre Galais, Aurélie Parzy, Salvatore Caruso, Jean François Codoul, Iulia Pripon, Mustapha Atlassi, Oana Cojocarasu, Etienne Suc, Ahmed Bedjaoui, Philippe Houyau, Yann Berge, Dany Gargot, Vincent Bourgeois, Pierre Emmanuel Henneresse, Sandrine Lavau denes, Valérie Lebrun Lyat, Dominique Genet, Jean Martin, Pr Pierre Michel, David Sefrioui, Anne Escande, Louis Marie Dourthe

Research output: Contribution to journal › Article › peer-review

8 Scopus citations

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% (H₁); 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.

Original language	English
Pages (from-to)	25-34
Number of pages	10
Journal	European Journal of Cancer
Volume	136
DOIs	https://doi.org/10.1016/j.ejca.2020.05.018
State	Published - Sep 2020
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2020 Elsevier Ltd

Keywords

FOLFIRI.3
Gemcitabine
Nab-paclitaxel
Pancreatic cancer
Sequential treatment

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Rinaldi, Y., Pointet, A. L., Khemissa Akouz, F., Le Malicot, K., Wahiba, B., Louafi, S., Gratet, A., Miglianico, L., Laharie, H., Bouhier Leporrier, K., Thirot Bidault, A., Texereau, P., Coriat, R., Terrebonne, E., Gouttebel, M. C., Malka, D., Bachet, J. B., Lepage, C., Taieb, J., ... Dourthe, L. M. (2020). 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). European Journal of Cancer, 136, 25-34. https://doi.org/10.1016/j.ejca.2020.05.018

Rinaldi, Yves ; Pointet, Anne Laure ; Khemissa Akouz, Faiza et al. / 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). In: European Journal of Cancer. 2020 ; Vol. 136. pp. 25-34.

@article{eeac4fd1d44045d482fda421d678bb7f,

title = "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 Canc{\'e}rologie Digestive-PRODIGE 37 randomised phase II study (FIRGEMAX)",

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% (H1); 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.",

keywords = "FOLFIRI.3, Gemcitabine, Nab-paclitaxel, Pancreatic cancer, Sequential treatment",

author = "Yves Rinaldi and Pointet, {Anne Laure} and {Khemissa Akouz}, Faiza and {Le Malicot}, Karine and Bidaut Wahiba and Samy Louafi and Alain Gratet and Laurent Miglianico and Hortense Laharie and {Bouhier Leporrier}, Karine and {Thirot Bidault}, Anne and Patrick Texereau and Romain Coriat and Eric Terrebonne and Gouttebel, {Marie Claude} and David Malka and Bachet, {Jean Baptiste} and C{\^o}me Lepage and Julien Taieb and C{\'e}cile Julien and Nicolas Barriere and Julie Gigout and Simon Pernot and C{\'e}line Lepere and Aziz Zaanan and G{\'e}raldine Perkins and Raymond Despax and J{\'e}r{\^o}me Chamois and Xavier Artignan and Pauline Regnault and Beno{\^i}t Dupont and Maxime Lesouef and {Bengrine Lefevre}, Leila and Julie Vincent and Fran{\c c}ois Ghiringhelli and Barbier, {Mme E.} and Morgan Andre and Johann Dreanic and Catherine Brezault-Bonnet and Val{\'e}rie Boige and Antoine Holllebecque and Bruno Valenza and Gildas Phelip and Philippe Dominici and Marion Chauvenet and Frederick Moryoussef and Etienne, {Pierre Luc} and Dominique Besson and Mathilde Martinez and Pamela Biondiani and Beno{\^i}t Avisse and Galais, {Marie Pierre} and Aur{\'e}lie Parzy and Salvatore Caruso and Codoul, {Jean Fran{\c c}ois} and Iulia Pripon and Mustapha Atlassi and Oana Cojocarasu and Etienne Suc and Ahmed Bedjaoui and Philippe Houyau and Yann Berge and Dany Gargot and Vincent Bourgeois and Henneresse, {Pierre Emmanuel} and {Lavau denes}, Sandrine and {Lebrun Lyat}, Val{\'e}rie and Dominique Genet and Jean Martin and Michel, {Pr Pierre} and David Sefrioui and Anne Escande and Dourthe, {Louis Marie}",

note = "Publisher Copyright: {\textcopyright} 2020 Elsevier Ltd",

year = "2020",

month = sep,

doi = "10.1016/j.ejca.2020.05.018",

language = "אנגלית",

volume = "136",

pages = "25--34",

journal = "European Journal of Cancer",

issn = "0959-8049",

publisher = "Elsevier Ltd.",

}

Rinaldi, Y, Pointet, AL, Khemissa Akouz, F, Le Malicot, K, Wahiba, B, Louafi, S, Gratet, A, Miglianico, L, Laharie, H, Bouhier Leporrier, K, Thirot Bidault, A, Texereau, P, Coriat, R, Terrebonne, E, Gouttebel, MC, Malka, D, Bachet, JB, Lepage, C, Taieb, J, Julien, C, Barriere, N, Gigout, J, Pernot, S, Lepere, C, Zaanan, A, Perkins, G, Despax, R, Chamois, J, Artignan, X, Regnault, P, Dupont, B, Lesouef, M, Bengrine Lefevre, L, Vincent, J, Ghiringhelli, F, Barbier, ME, Andre, M, Dreanic, J, Brezault-Bonnet, C, Boige, V, Holllebecque, A, Valenza, B, Phelip, G, Dominici, P, Chauvenet, M, Moryoussef, F, Etienne, PL, Besson, D, Martinez, M, Biondiani, P, Avisse, B, Galais, MP, Parzy, A, Caruso, S, Codoul, JF, Pripon, I, Atlassi, M, Cojocarasu, O, Suc, E, Bedjaoui, A, Houyau, P, Berge, Y, Gargot, D, Bourgeois, V, Henneresse, PE, Lavau denes, S, Lebrun Lyat, V, Genet, D, Martin, J, Michel, PP, Sefrioui, D, Escande, A & Dourthe, LM 2020, '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)', European Journal of Cancer, vol. 136, pp. 25-34. https://doi.org/10.1016/j.ejca.2020.05.018

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). / Rinaldi, Yves; Pointet, Anne Laure; Khemissa Akouz, Faiza et al.
In: European Journal of Cancer, Vol. 136, 09.2020, p. 25-34.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Gemcitabine plus nab-paclitaxel until progression or alternating with FOLFIRI.3, as first-line treatment for patients with metastatic pancreatic adenocarcinoma

T2 - The Federation Francophone de Cancérologie Digestive-PRODIGE 37 randomised phase II study (FIRGEMAX)

AU - Rinaldi, Yves

AU - Pointet, Anne Laure

AU - Khemissa Akouz, Faiza

AU - Le Malicot, Karine

AU - Wahiba, Bidaut

AU - Louafi, Samy

AU - Gratet, Alain

AU - Miglianico, Laurent

AU - Laharie, Hortense

AU - Bouhier Leporrier, Karine

AU - Thirot Bidault, Anne

AU - Texereau, Patrick

AU - Coriat, Romain

AU - Terrebonne, Eric

AU - Gouttebel, Marie Claude

AU - Malka, David

AU - Bachet, Jean Baptiste

AU - Lepage, Côme

AU - Taieb, Julien

AU - Julien, Cécile

AU - Barriere, Nicolas

AU - Gigout, Julie

AU - Pernot, Simon

AU - Lepere, Céline

AU - Zaanan, Aziz

AU - Perkins, Géraldine

AU - Despax, Raymond

AU - Chamois, Jérôme

AU - Artignan, Xavier

AU - Regnault, Pauline

AU - Dupont, Benoît

AU - Lesouef, Maxime

AU - Bengrine Lefevre, Leila

AU - Vincent, Julie

AU - Ghiringhelli, François

AU - Barbier, Mme E.

AU - Andre, Morgan

AU - Dreanic, Johann

AU - Brezault-Bonnet, Catherine

AU - Boige, Valérie

AU - Holllebecque, Antoine

AU - Valenza, Bruno

AU - Phelip, Gildas

AU - Dominici, Philippe

AU - Chauvenet, Marion

AU - Moryoussef, Frederick

AU - Etienne, Pierre Luc

AU - Besson, Dominique

AU - Martinez, Mathilde

AU - Biondiani, Pamela

AU - Avisse, Benoît

AU - Galais, Marie Pierre

AU - Parzy, Aurélie

AU - Caruso, Salvatore

AU - Codoul, Jean François

AU - Pripon, Iulia

AU - Atlassi, Mustapha

AU - Cojocarasu, Oana

AU - Suc, Etienne

AU - Bedjaoui, Ahmed

AU - Houyau, Philippe

AU - Berge, Yann

AU - Gargot, Dany

AU - Bourgeois, Vincent

AU - Henneresse, Pierre Emmanuel

AU - Lavau denes, Sandrine

AU - Lebrun Lyat, Valérie

AU - Genet, Dominique

AU - Martin, Jean

AU - Michel, Pr Pierre

AU - Sefrioui, David

AU - Escande, Anne

AU - Dourthe, Louis Marie

PY - 2020/9

Y1 - 2020/9

N2 - 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% (H1); 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.

AB - 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% (H1); 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.

KW - FOLFIRI.3

KW - Gemcitabine

KW - Nab-paclitaxel

KW - Pancreatic cancer

KW - Sequential treatment

UR - http://www.scopus.com/inward/record.url?scp=85087215202&partnerID=8YFLogxK

U2 - 10.1016/j.ejca.2020.05.018

DO - 10.1016/j.ejca.2020.05.018

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

C2 - 32623182

AN - SCOPUS:85087215202

SN - 0959-8049

VL - 136

SP - 25

EP - 34

JO - European Journal of Cancer

JF - European Journal of Cancer

ER -

Rinaldi Y, Pointet AL, Khemissa Akouz F, Le Malicot K, Wahiba B, Louafi S et al. 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). European Journal of Cancer. 2020 Sep;136:25-34. doi: 10.1016/j.ejca.2020.05.018

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)

Abstract

Bibliographical note

Keywords

UN SDGs

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