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 & 28 others 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

Research output: Contribution to journalReview articleAcademicpeer-review

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 languageEnglish
Pages (from-to)782-794
JournalJournal of the National Cancer Institute
Volume111
Issue number8
DOIs
Publication statusPublished - 1 Aug 2019
Externally publishedYes

Cite this

Janssen, Quisette P. ; Buettner, Stefan ; Suker, Mustafa ; Beumer, Berend R. ; Addeo, Pietro ; Bachellier, Philippe ; Bahary, Nathan ; Bekaii-Saab, Tanios ; Bali, Maria A. ; Besselink, Marc G. ; Boone, Brian A. ; Chau, Ian ; Clarke, Stephen ; Dillhoff, Mary ; el-Rayes, Bassel F. ; Frakes, Jessica M. ; Grose, Derek ; Hosein, Peter J. ; Jamieson, Nigel B. ; Javed, Ammar A. ; Khan, Khurum ; Kim, Kyu-Pyo ; Kim, Song Cheol ; Kim, Sunhee S. ; Ko, Andrew H. ; Lacy, Jill ; Margonis, Georgios A. ; McCarter, Martin D. ; McKay, Colin J. ; Mellon, Eric A. ; Moorcraft, Sing Yu ; Okada, Ken-Ichi ; Paniccia, Alessandro ; Parikh, Parag J. ; Peters, Niek A. ; Rabl, Hans ; Samra, Jaswinder ; Tinchon, Christoph ; van Tienhoven, Geertjan ; van Veldhuisen, Eran ; Wang-Gillam, Andrea ; Weiss, Matthew J. ; Wilmink, Johanna W. ; Yamaue, Hiroki ; Homs, Marjolein Y. V. ; van Eijck, Casper H. J. ; Katz, Matthew H. G. ; Groot Koerkamp, Bas. / Neoadjuvant FOLFIRINOX in Patients with Borderline Resectable Pancreatic Cancer: A Systematic Review and Patient-Level Meta-Analysis. In: Journal of the National Cancer Institute. 2019 ; Vol. 111, No. 8. pp. 782-794.
@article{824ebc0d76494ece857499ac373db95f,
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 Kyu-Pyo Kim 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 Ken-Ichi Okada 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 {Groot Koerkamp}, Bas",
year = "2019",
month = "8",
day = "1",
doi = "10.1093/jnci/djz073",
language = "English",
volume = "111",
pages = "782--794",
journal = "Journal of the National Cancer Institute",
issn = "0027-8874",
publisher = "Oxford University Press",
number = "8",

}

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, K-P, Kim, SC, Kim, SS, Ko, AH, Lacy, J, Margonis, GA, McCarter, MD, McKay, CJ, Mellon, EA, Moorcraft, SY, Okada, K-I, 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 & Groot Koerkamp, B 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

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

In: Journal of the National Cancer Institute, Vol. 111, No. 8, 01.08.2019, p. 782-794.

Research output: Contribution to journalReview articleAcademicpeer-review

TY - JOUR

T1 - Neoadjuvant FOLFIRINOX in Patients with Borderline Resectable Pancreatic Cancer: 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 - Groot Koerkamp, Bas

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.

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UR - https://www.ncbi.nlm.nih.gov/pubmed/31086963

U2 - 10.1093/jnci/djz073

DO - 10.1093/jnci/djz073

M3 - Review article

VL - 111

SP - 782

EP - 794

JO - Journal of the National Cancer Institute

JF - Journal of the National Cancer Institute

SN - 0027-8874

IS - 8

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