A Systematic Review and Meta-Analysis of Folfirinox (FFX) vs Gemcitabine Plus Nab-Paclitaxel (GnP) as the Initial Treatment for Pancreatic Cancer (PC)

Introduction: The establishment of Folfirinox (FFX) or Gemcitabine + Nab Paclitaxel (GnP) as first-line treatments for pancreatic cancer (PC) is still under investigation. To evaluate their effectiveness and safety, we analyzed retrospective studies, comparing the survival and safety outcomes of these 2 regimens in PC patients Methods: We conducted an extensive review of 2 electronic databases from inception till February 2023 to include all the relevant studies that compared FFX with GnP published and unpublished work. Retrospective studies were only included. Over-all survival (OS) and progression free survival (PFS) were pooled using hazard ratios (HR) while Objective response rate (ORR) and safety outcomes were pooled using odds ratios (OR) with 95% CI using the random effects model Results: A total of 7,030 patients were identified in a total of 21 articles that were shortlisted. Pooled results concluded that neither FFX nor GnP were associated to increase the OS time (HR 0.93, 95% CI 0.83- 1.04; P=0.0001) however FFX was more likely associated with increased PFS when compared to GnP (HR 0.88, 95 % CI 0.81- 0.97; P< 0.0001). ORR proved to be non-significant between the 2 regimens (OR 0.90, 95% CI 0.64- 1.27; P=0.15). Safety outcomes included neutropenia, anemia, thrombocytopenia and diarrhea. GnP was more associated with diarrhea (OR 1.96, 95% CI 1.22- 3.15; P= 0.001) while FFX was seen to cause anemia (OR 0.70, 95% CI 0.51- 0.98 P=0.10) in PC patients. Neutropenia and thrombocytopenia were in-significant in the 2 drug regimens (OR 1.10, 95% CI 0.92- 1.31; P= 0.33) and (OR 0.83, 95% CI 0.60- 1.13; P=0.23) respectively (Figure 1, Table 1). Conclusion: FFX and GnP showed a significant difference in increasing the PFS while no difference was observed while measuring OS. Safety outcomes showed that FFX and GnP shared similar safety profiles as FFX was associated with Hematological outcomes while GnP was more associated with non-hematological outcomes.Figure 1.: Forest plot over-all survival (HR 0.93, 95% CI 0.83- 1.04; P=0.0001). Table 1. - USA= United states of America, PS= Performance status, NA=Not applicable, GEM-NAB= Gemcitabine+ Nab paclitaxel Author Year of publication Country Start Time End Time PS Number of patients Median age Males (%) Median follow-up treatment Nakazawa, J. 2019 Japan 2013.12 2018.6 0-2 92 68 NA 14.9 months (0.7-30.9) GEM-NAB 119 61 NA 13.1 months (1.3-40.8) FOLFIRINOX Kim, S 2018 USA 2015.4 2015.12 0-4 337 64.59 64.7% 10.7 months GEM-NAB 317 59.03 67.2% FOLFIRINOX Muranaka, T. 2017 Japan 2013.12 2015.9 0-1 22 66.5 54.5% 8.3 months GEM-NAB 16 63 62.5% 11.9 months FOLFIRINOX Papneja, N. 2019 Canada 2011 2016 0-3 33 #211E1E;64 #211E1E;52% 8 months GEM-NAB 86 #211E1E;59 #211E1E;62% FOLFIRINOX Cho, I 2018 Korea 2015 NA NA 81 54 NA 7.9 months (1.5-23.4) GEM-NAB 86 65 NA FOLFIRINOX Williet, N. 2019 France 2015.6 2018.6 0-2 109 68.1 49.5% NA GEM-NAB 107 61.8 59.8% FOLFIRINOX Chan, K.K.W 2019 Canada 2015.4 2017.3 NA 498 69.14 60.2% NA GEM-NAB 632 61.83 54.6% FOLFIRINOX Barrera, I. 2019 Canada 2010 2018 NA 41 NA NA NA GEM-NAB 60 NA NA FOLFIRINOX 60 NA NA GEM Longo Muñoz, F. 2019 Spain 2011.1 2018.5 NA NA NA NA NA GEM-NAB Chun JW 2021 Korea 2011.5 2019.3 0-2 151 64 60.3% 33 months GEM-NAB 151 62 55.6% FOLFIRINOX Rapposelli IG 2021 NA 2014.1 2020.12 0-2 268 62 61.9% 21.8 months GEM-NAB 171 61 62% FOLFIRINOX Lee JC 2020 South Korea 2011.7 2017.12 0-2 181 69 53% NA GEM-NAB 232 60 61% FOLFIRINOX Riedl JM 2021 Austria 2010.8 2019.10 0-1 297 70 59% 26.2 months GEM-NAB 158 63 59% FOLFIRINOX Sigel K 2022 NA 2003 2016 NA 317 66 98% NA GEM-NAB 353 61 94% FOLFIRINOX Ay S 2022 NA 2010.1 2020.12 0-1 79 61 49.4% NA GEM-NAB 103 58 60.2% FOLFIRINOX Santucci J 2022 Australia & New Zealand 2016 2020 0-4 375 67 52.7% 8.7 months GEM-NAB 73 59 60.3% 6.3 months FOLFIRINOX Yoshida Y 2022 Japan 2001.4 2017.12 0-2 28 62.5 57.1% 9.4 months GEM-NAB 10 56.5 90% FOLFIRINOX Pijnappel EN 2022 Netherlands 2015 2018 0-4 207 69 50% 4.1 months GEM-NAB 1029 62 54% FOLFIRINOX Arima S 2021 Japan 2013.12 2017.3 0-2 47 68 61.7% 14.2 months GEM-NAB 16 65 56.3% FOLFIRINOX Templeton S 2020 Canada 2011 2017 0-1 10 66.9 70% 15 months GEM-NAB 10 62.6 70% FOLFIRINOX Servetto A 2022 Italy 2011.2 2020.11 0-1 117 63.7 57.3% NA GEM-NAB 43 53.6 65.1% FOLFIRINOX