Neoadjuvant FOLFIRINOX in patients with borderline resectable pancreatic cancer: A systematic review and patient-level meta-analysis

Quisette P. Janssen; Stefan Buettner; Mustafa Suker; Berend R. Beumer; Pietro Addeo; Philippe Bachellier; Nathan Bahary; Tanios Bekaii-Saab; Maria A. Bali; Marc G. Besselink; Brian A. Boone; Ian Chau; Stephen Clarke; Mary Dillhoff; Bassel F. El-Rayes; Jessica M. Frakes; Derek Grose; Peter J. Hosein; Nigel B. Jamieson; Ammar A. Javed; Khurum Khan; Kyu Pyo Kim; Song Cheol Kim; Sunhee S. Kim; Andrew H. Ko; Jill Lacy; Georgios A. Margonis; Martin D. McCarter; Colin J. McKay; Eric A. Mellon; Sing Yu Moorcraft; Ken Ichi Okada; Alessandro Paniccia; Parag J. Parikh; Niek A. Peters; Hans Rabl; Jaswinder Samra; Christoph Tinchon; Geertjan van Tienhoven; Eran van Veldhuisen; Andrea Wang-Gillam; Matthew J. Weiss; Johanna W. Wilmink; Hiroki Yamaue; Marjolein Y.V. Homs; Casper H.J. van Eijck; Matthew H.G. Katz; Bas Groot Koerkamp

doi:10.1093/jnci/djz073

Neoadjuvant FOLFIRINOX in patients with borderline resectable pancreatic cancer: A systematic review and patient-level meta-analysis

Quisette P. Janssen, Stefan Buettner, Mustafa Suker, Berend R. Beumer, Pietro Addeo, Philippe Bachellier, Nathan Bahary, Tanios Bekaii-Saab, Maria A. Bali, Marc G. Besselink, Brian A. Boone, Ian Chau, Stephen Clarke, Mary Dillhoff, Bassel F. El-Rayes, Jessica M. Frakes, Derek Grose, Peter J. Hosein, Nigel B. Jamieson, Ammar A. JavedKhurum Khan, Kyu Pyo Kim, Song Cheol Kim, Sunhee S. Kim, Andrew H. Ko, Jill Lacy, Georgios A. Margonis, Martin D. McCarter, Colin J. McKay, Eric A. Mellon, Sing Yu Moorcraft, Ken Ichi Okada, Alessandro Paniccia, Parag J. Parikh, Niek A. Peters, Hans Rabl, Jaswinder Samra, Christoph Tinchon, Geertjan van Tienhoven, Eran van Veldhuisen, Andrea Wang-Gillam, Matthew J. Weiss, Johanna W. Wilmink, Hiroki Yamaue, Marjolein Y.V. Homs, Casper H.J. van Eijck, Matthew H.G. Katz, Bas Groot Koerkamp

Hematology/Oncology

Research output: Contribution to journal › Review article › peer-review

62 Scopus citations

Abstract

FOLFIRINOX is a standard treatment for metastatic pancreatic cancer patients. The effectiveness of neoadjuvant FOLFIRINOX in patients with borderline resectable pancreatic cancer (BRPC) remains debated. Methods: We performed a systematic review and patient-level meta-analysis on neoadjuvant FOLFIRINOX in patients with BRPC. Studies with BRPC patients who received FOLFIRINOX as first-line neoadjuvant treatment were included. The primary endpoint was overall survival (OS), and secondary endpoints were progression-free survival, resection rate, R0 resection rate, and grade III-IV adverse events. Patient-level survival outcomes were obtained from authors of the included studies and analyzed using the Kaplan-Meier method. Results: We included 24 studies (8 prospective, 16 retrospective), comprising 313 (38.1%) BRPC patients treated with FOLFIRINOX. Most studies (n = 20) presented intention-to-treat results. The median number of administered neoadjuvant FOLFIRINOX cycles ranged from 4 to 9. The resection rate was 67.8% (95% confidence interval [CI] = 60.1% to 74.6%), and the R0-resection rate was 83.9% (95% CI = 76.8% to 89.1%). The median OS varied from 11.0 to 34.2 months across studies. Patient-level survival data were obtained for 20 studies representing 283 BRPC patients. The patient-level median OS was 22.2 months (95% CI = 18.8 to 25.6 months), and patient-level median progression-free survival was 18.0 months (95% CI = 14.5 to 21.5 months). Pooled event rates for grade III-IV adverse events were highest for neutropenia (17.5 per 100 patients, 95% CI = 10.3% to 28.3%), diarrhea (11.1 per 100 patients, 95% CI = 8.6 to 14.3), and fatigue (10.8 per 100 patients, 95% CI = 8.1 to 14.2). No deaths were attributed to FOLFIRINOX. Conclusions: This patient-level meta-analysis of BRPC patients treated with neoadjuvant FOLFIRINOX showed a favorable median OS, resection rate, and R0-resection rate. These results need to be assessed in a randomized trial.

Original language	English (US)
Pages (from-to)	782-794
Number of pages	13
Journal	Journal of the National Cancer Institute
Volume	111
Issue number	8
DOIs	https://doi.org/10.1093/jnci/djz073
State	Published - Aug 1 2019

ASJC Scopus subject areas

Oncology
Cancer Research

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10.1093/jnci/djz073

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Janssen, Q. P., Buettner, S., Suker, M., Beumer, B. R., Addeo, P., Bachellier, P., Bahary, N., Bekaii-Saab, T., Bali, M. A., Besselink, M. G., Boone, B. A., Chau, I., Clarke, S., Dillhoff, M., El-Rayes, B. F., Frakes, J. M., Grose, D., Hosein, P. J., Jamieson, N. B., ... Koerkamp, B. G. (2019). Neoadjuvant FOLFIRINOX in patients with borderline resectable pancreatic cancer: A systematic review and patient-level meta-analysis. Journal of the National Cancer Institute, 111(8), 782-794. https://doi.org/10.1093/jnci/djz073

Janssen, QP, Buettner, S, Suker, M, Beumer, BR, Addeo, P, Bachellier, P, Bahary, N, Bekaii-Saab, T, Bali, MA, Besselink, MG, Boone, BA, Chau, I, Clarke, S, Dillhoff, M, El-Rayes, BF, Frakes, JM, Grose, D, Hosein, PJ, Jamieson, NB, Javed, AA, Khan, K, Kim, KP, Kim, SC, Kim, SS, Ko, AH, Lacy, J, Margonis, GA, McCarter, MD, McKay, CJ, Mellon, EA, Moorcraft, SY, Okada, KI, Paniccia, A, Parikh, PJ, Peters, NA, Rabl, H, Samra, J, Tinchon, C, van Tienhoven, G, van Veldhuisen, E, Wang-Gillam, A, Weiss, MJ, Wilmink, JW, Yamaue, H, Homs, MYV, van Eijck, CHJ, Katz, MHG & Koerkamp, BG 2019, 'Neoadjuvant FOLFIRINOX in patients with borderline resectable pancreatic cancer: A systematic review and patient-level meta-analysis', Journal of the National Cancer Institute, vol. 111, no. 8, pp. 782-794. https://doi.org/10.1093/jnci/djz073

@article{2076e76cea964281962c3a1d6008db97,

title = "Neoadjuvant FOLFIRINOX in patients with borderline resectable pancreatic cancer: A systematic review and patient-level meta-analysis",

abstract = "FOLFIRINOX is a standard treatment for metastatic pancreatic cancer patients. The effectiveness of neoadjuvant FOLFIRINOX in patients with borderline resectable pancreatic cancer (BRPC) remains debated. Methods: We performed a systematic review and patient-level meta-analysis on neoadjuvant FOLFIRINOX in patients with BRPC. Studies with BRPC patients who received FOLFIRINOX as first-line neoadjuvant treatment were included. The primary endpoint was overall survival (OS), and secondary endpoints were progression-free survival, resection rate, R0 resection rate, and grade III-IV adverse events. Patient-level survival outcomes were obtained from authors of the included studies and analyzed using the Kaplan-Meier method. Results: We included 24 studies (8 prospective, 16 retrospective), comprising 313 (38.1%) BRPC patients treated with FOLFIRINOX. Most studies (n = 20) presented intention-to-treat results. The median number of administered neoadjuvant FOLFIRINOX cycles ranged from 4 to 9. The resection rate was 67.8% (95% confidence interval [CI] = 60.1% to 74.6%), and the R0-resection rate was 83.9% (95% CI = 76.8% to 89.1%). The median OS varied from 11.0 to 34.2 months across studies. Patient-level survival data were obtained for 20 studies representing 283 BRPC patients. The patient-level median OS was 22.2 months (95% CI = 18.8 to 25.6 months), and patient-level median progression-free survival was 18.0 months (95% CI = 14.5 to 21.5 months). Pooled event rates for grade III-IV adverse events were highest for neutropenia (17.5 per 100 patients, 95% CI = 10.3% to 28.3%), diarrhea (11.1 per 100 patients, 95% CI = 8.6 to 14.3), and fatigue (10.8 per 100 patients, 95% CI = 8.1 to 14.2). No deaths were attributed to FOLFIRINOX. Conclusions: This patient-level meta-analysis of BRPC patients treated with neoadjuvant FOLFIRINOX showed a favorable median OS, resection rate, and R0-resection rate. These results need to be assessed in a randomized trial.",

author = "Janssen, {Quisette P.} and Stefan Buettner and Mustafa Suker and Beumer, {Berend R.} and Pietro Addeo and Philippe Bachellier and Nathan Bahary and Tanios Bekaii-Saab and Bali, {Maria A.} and Besselink, {Marc G.} and Boone, {Brian A.} and Ian Chau and Stephen Clarke and Mary Dillhoff and El-Rayes, {Bassel F.} and Frakes, {Jessica M.} and Derek Grose and Hosein, {Peter J.} and Jamieson, {Nigel B.} and Javed, {Ammar A.} and Khurum Khan and Kim, {Kyu Pyo} and Kim, {Song Cheol} and Kim, {Sunhee S.} and Ko, {Andrew H.} and Jill Lacy and Margonis, {Georgios A.} and McCarter, {Martin D.} and McKay, {Colin J.} and Mellon, {Eric A.} and Moorcraft, {Sing Yu} and Okada, {Ken Ichi} and Alessandro Paniccia and Parikh, {Parag J.} and Peters, {Niek A.} and Hans Rabl and Jaswinder Samra and Christoph Tinchon and {van Tienhoven}, Geertjan and {van Veldhuisen}, Eran and Andrea Wang-Gillam and Weiss, {Matthew J.} and Wilmink, {Johanna W.} and Hiroki Yamaue and Homs, {Marjolein Y.V.} and {van Eijck}, {Casper H.J.} and Katz, {Matthew H.G.} and Koerkamp, {Bas Groot}",

note = "Funding Information: MD received educational support from Intuitive; EAM received travel funding from ViewRay; SC received travel funding from AstraZeneca, Roche, BMS, and Ipsen and is a member of the advisory boards of AstraZeneca, Roche, BMS, Ipsen, and Specialised Therapeutics Australia; PJH received research funding from AstraZeneca and Kite and is a member of the advisory boards of Ipsen and Angiodynamics; BFE-R received research funding from Boston Biomedical, Bayer, Pfizer, Novartis, Merck, BMS, and Roche and serves as a consultant for Astellas, Taiho, Ipsen, Novartis, Lexicon, and Roche; AW-G serves as consultant for Tyme; MM received research funding from Merck; SCK received research funding from the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (HI14C2640). The other authors have no competing interests to declare. Funding Information: This work was supported by the Dutch Cancer Society (grant 2017-109555) and The Netherlands Organisation for Health Research and Development (grant 2017-8430041 08). Publisher Copyright: {\textcopyright} 2019 The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.",

year = "2019",

month = aug,

day = "1",

doi = "10.1093/jnci/djz073",

language = "English (US)",

volume = "111",

pages = "782--794",

journal = "Journal of the National Cancer Institute",

issn = "0027-8874",

publisher = "Oxford University Press",

number = "8",

}

TY - JOUR

T1 - Neoadjuvant FOLFIRINOX in patients with borderline resectable pancreatic cancer

T2 - A systematic review and patient-level meta-analysis

AU - Janssen, Quisette P.

AU - Buettner, Stefan

AU - Suker, Mustafa

AU - Beumer, Berend R.

AU - Addeo, Pietro

AU - Bachellier, Philippe

AU - Bahary, Nathan

AU - Bekaii-Saab, Tanios

AU - Bali, Maria A.

AU - Besselink, Marc G.

AU - Boone, Brian A.

AU - Chau, Ian

AU - Clarke, Stephen

AU - Dillhoff, Mary

AU - El-Rayes, Bassel F.

AU - Frakes, Jessica M.

AU - Grose, Derek

AU - Hosein, Peter J.

AU - Jamieson, Nigel B.

AU - Javed, Ammar A.

AU - Khan, Khurum

AU - Kim, Kyu Pyo

AU - Kim, Song Cheol

AU - Kim, Sunhee S.

AU - Ko, Andrew H.

AU - Lacy, Jill

AU - Margonis, Georgios A.

AU - McCarter, Martin D.

AU - McKay, Colin J.

AU - Mellon, Eric A.

AU - Moorcraft, Sing Yu

AU - Okada, Ken Ichi

AU - Paniccia, Alessandro

AU - Parikh, Parag J.

AU - Peters, Niek A.

AU - Rabl, Hans

AU - Samra, Jaswinder

AU - Tinchon, Christoph

AU - van Tienhoven, Geertjan

AU - van Veldhuisen, Eran

AU - Wang-Gillam, Andrea

AU - Weiss, Matthew J.

AU - Wilmink, Johanna W.

AU - Yamaue, Hiroki

AU - Homs, Marjolein Y.V.

AU - van Eijck, Casper H.J.

AU - Katz, Matthew H.G.

AU - Koerkamp, Bas Groot

N1 - Funding Information: MD received educational support from Intuitive; EAM received travel funding from ViewRay; SC received travel funding from AstraZeneca, Roche, BMS, and Ipsen and is a member of the advisory boards of AstraZeneca, Roche, BMS, Ipsen, and Specialised Therapeutics Australia; PJH received research funding from AstraZeneca and Kite and is a member of the advisory boards of Ipsen and Angiodynamics; BFE-R received research funding from Boston Biomedical, Bayer, Pfizer, Novartis, Merck, BMS, and Roche and serves as a consultant for Astellas, Taiho, Ipsen, Novartis, Lexicon, and Roche; AW-G serves as consultant for Tyme; MM received research funding from Merck; SCK received research funding from the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (HI14C2640). The other authors have no competing interests to declare. Funding Information: This work was supported by the Dutch Cancer Society (grant 2017-109555) and The Netherlands Organisation for Health Research and Development (grant 2017-8430041 08). Publisher Copyright: © 2019 The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

PY - 2019/8/1

Y1 - 2019/8/1

N2 - FOLFIRINOX is a standard treatment for metastatic pancreatic cancer patients. The effectiveness of neoadjuvant FOLFIRINOX in patients with borderline resectable pancreatic cancer (BRPC) remains debated. Methods: We performed a systematic review and patient-level meta-analysis on neoadjuvant FOLFIRINOX in patients with BRPC. Studies with BRPC patients who received FOLFIRINOX as first-line neoadjuvant treatment were included. The primary endpoint was overall survival (OS), and secondary endpoints were progression-free survival, resection rate, R0 resection rate, and grade III-IV adverse events. Patient-level survival outcomes were obtained from authors of the included studies and analyzed using the Kaplan-Meier method. Results: We included 24 studies (8 prospective, 16 retrospective), comprising 313 (38.1%) BRPC patients treated with FOLFIRINOX. Most studies (n = 20) presented intention-to-treat results. The median number of administered neoadjuvant FOLFIRINOX cycles ranged from 4 to 9. The resection rate was 67.8% (95% confidence interval [CI] = 60.1% to 74.6%), and the R0-resection rate was 83.9% (95% CI = 76.8% to 89.1%). The median OS varied from 11.0 to 34.2 months across studies. Patient-level survival data were obtained for 20 studies representing 283 BRPC patients. The patient-level median OS was 22.2 months (95% CI = 18.8 to 25.6 months), and patient-level median progression-free survival was 18.0 months (95% CI = 14.5 to 21.5 months). Pooled event rates for grade III-IV adverse events were highest for neutropenia (17.5 per 100 patients, 95% CI = 10.3% to 28.3%), diarrhea (11.1 per 100 patients, 95% CI = 8.6 to 14.3), and fatigue (10.8 per 100 patients, 95% CI = 8.1 to 14.2). No deaths were attributed to FOLFIRINOX. Conclusions: This patient-level meta-analysis of BRPC patients treated with neoadjuvant FOLFIRINOX showed a favorable median OS, resection rate, and R0-resection rate. These results need to be assessed in a randomized trial.

AB - FOLFIRINOX is a standard treatment for metastatic pancreatic cancer patients. The effectiveness of neoadjuvant FOLFIRINOX in patients with borderline resectable pancreatic cancer (BRPC) remains debated. Methods: We performed a systematic review and patient-level meta-analysis on neoadjuvant FOLFIRINOX in patients with BRPC. Studies with BRPC patients who received FOLFIRINOX as first-line neoadjuvant treatment were included. The primary endpoint was overall survival (OS), and secondary endpoints were progression-free survival, resection rate, R0 resection rate, and grade III-IV adverse events. Patient-level survival outcomes were obtained from authors of the included studies and analyzed using the Kaplan-Meier method. Results: We included 24 studies (8 prospective, 16 retrospective), comprising 313 (38.1%) BRPC patients treated with FOLFIRINOX. Most studies (n = 20) presented intention-to-treat results. The median number of administered neoadjuvant FOLFIRINOX cycles ranged from 4 to 9. The resection rate was 67.8% (95% confidence interval [CI] = 60.1% to 74.6%), and the R0-resection rate was 83.9% (95% CI = 76.8% to 89.1%). The median OS varied from 11.0 to 34.2 months across studies. Patient-level survival data were obtained for 20 studies representing 283 BRPC patients. The patient-level median OS was 22.2 months (95% CI = 18.8 to 25.6 months), and patient-level median progression-free survival was 18.0 months (95% CI = 14.5 to 21.5 months). Pooled event rates for grade III-IV adverse events were highest for neutropenia (17.5 per 100 patients, 95% CI = 10.3% to 28.3%), diarrhea (11.1 per 100 patients, 95% CI = 8.6 to 14.3), and fatigue (10.8 per 100 patients, 95% CI = 8.1 to 14.2). No deaths were attributed to FOLFIRINOX. Conclusions: This patient-level meta-analysis of BRPC patients treated with neoadjuvant FOLFIRINOX showed a favorable median OS, resection rate, and R0-resection rate. These results need to be assessed in a randomized trial.

UR - http://www.scopus.com/inward/record.url?scp=85072894072&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85072894072&partnerID=8YFLogxK

U2 - 10.1093/jnci/djz073

DO - 10.1093/jnci/djz073

M3 - Review article

C2 - 31086963

AN - SCOPUS:85072894072

SN - 0027-8874

VL - 111

SP - 782

EP - 794

JO - Journal of the National Cancer Institute

JF - Journal of the National Cancer Institute

IS - 8

ER -

Neoadjuvant FOLFIRINOX in patients with borderline resectable pancreatic cancer: A systematic review and patient-level meta-analysis

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