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Meta-Analysis
. 2019 Aug 1;111(8):782-794.
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  1 , Stefan Buettner  1 , Mustafa Suker  1 , Berend R Beumer  1 , Pietro Addeo  1 , Philippe Bachellier  1 , Nathan Bahary  1 , Tanios Bekaii-Saab  1 , Maria A Bali  1 , Marc G Besselink  1 , Brian A Boone  1 , Ian Chau  1 , Stephen Clarke  1 , Mary Dillhoff  1 , Bassel F El-Rayes  1 , Jessica M Frakes  1 , Derek Grose  1 , Peter J Hosein  1 , Nigel B Jamieson  1 , Ammar A Javed  1 , Khurum Khan  1 , Kyu-Pyo Kim  1 , Song Cheol Kim  1 , Sunhee S Kim  1 , Andrew H Ko  1 , Jill Lacy  1 , Georgios A Margonis  1 , Martin D McCarter  1 , Colin J McKay  1 , Eric A Mellon  1 , Sing Yu Moorcraft  1 , Ken-Ichi Okada  1 , Alessandro Paniccia  1 , Parag J Parikh  1 , Niek A Peters  1 , Hans Rabl  1 , Jaswinder Samra  1 , Christoph Tinchon  1 , Geertjan van Tienhoven  1 , Eran van Veldhuisen  1 , Andrea Wang-Gillam  1 , Matthew J Weiss  1 , Johanna W Wilmink  1 , Hiroki Yamaue  1 , Marjolein Y V Homs  1 , Casper H J van Eijck  1 , Matthew H G Katz  1 , Bas Groot Koerkamp  1
Affiliations
Meta-Analysis

Neoadjuvant FOLFIRINOX in Patients With Borderline Resectable Pancreatic Cancer: A Systematic Review and Patient-Level Meta-Analysis

Quisette P Janssen et al. J Natl Cancer Inst. .

Abstract

Background: 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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Figures

Figure 1.
Figure 1.
PRISMA flow chart showing selection of articles for systematic review and meta-analysis. (B)RPC = (borderline) resectable pancreatic cancer.
Figure 2.
Figure 2.
Pooled and patient-level overall survival (OS) and progression-free survival (PFS). Pooled and patient-level (A) OS and (B) pooled and patient-level PFS were analyzed. Patient-level survival outcomes were calculated from treatment initiation and analyzed using the Kaplan-Meier method. The Kaplan-Meier method was used to account for censoring of patients alive or without recurrence at last follow-up. Pooled median OS was 22.2 months (95% confidence interval [CI] = 18.8 to 25.6 months). Pooled median PFS was 18.0 months (95% CI = 14.5 to 21.5 months).
Figure 2.
Figure 2.
Pooled and patient-level overall survival (OS) and progression-free survival (PFS). Pooled and patient-level (A) OS and (B) pooled and patient-level PFS were analyzed. Patient-level survival outcomes were calculated from treatment initiation and analyzed using the Kaplan-Meier method. The Kaplan-Meier method was used to account for censoring of patients alive or without recurrence at last follow-up. Pooled median OS was 22.2 months (95% confidence interval [CI] = 18.8 to 25.6 months). Pooled median PFS was 18.0 months (95% CI = 14.5 to 21.5 months).
Figure 3.
Figure 3.
Pooled overall survival for patients with borderline resectable, locally advanced, and metastatic pancreatic cancer. For the survival curve of the locally advanced pancreatic cancer patients, patient-level data from the meta-analysis Suker et al. (49) was used. For the estimation of the survival curve for the metastatic pancreatic cancer patients, data were extracted from the graph of Conroy et al. (11).
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