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

Research output: Contribution to journalReview articlepeer-review

40 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 languageEnglish (US)
Pages (from-to)782-794
Number of pages13
JournalJournal of the National Cancer Institute
Volume111
Issue number8
DOIs
StatePublished - Aug 1 2019

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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