Top

BMC Cancer

Published in:

Open Access 01-12-2021 | Pancreatic Cancer | Research article

Meta-analysis and indirect treatment comparison of modified FOLFIRINOX and gemcitabine plus nab-paclitaxel as first-line chemotherapy in advanced pancreatic cancer

Authors: Jiayuan Chen, Qingling Hua, Haihong Wang, Dejun Zhang, Lei Zhao, Dandan Yu, Guoliang Pi, Tao Zhang, Zhenyu Lin

Published in: BMC Cancer | Issue 1/2021

Abstract

Background

Modified FOLFIRINOX and gemcitabine plus nab-paclitaxel (GEM-NAB) have been recommended as first-line therapies for advanced pancreatic cancer (PC). Due to the lack of evidence to directly compare them, we conducted this network meta-analysis to indirectly compare the effectiveness and toxicity of modified FOLFIRINOX and GEM-NAB.

Methods

The eligible retrospective studies on treatments related to modified FOLFIRINOX and GEM-NAB up to 4 April 2020 were searched and assessed. We used the frequentist model to analyze the survival and toxicity data between different treatments. Pooled analysis for overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and events of toxicity were analyzed in this study.

Results

Twenty-two studies were involved in this network meta-analysis. The comparisons on OS and PFS showed that modified FOLFIRINOX and GEM-NAB had similar treatment efficacy (OS: 1.13; 95% CI: 0.78–1.63; PFS: HR: 1.19; 95% CI: 0.85–1.67). GEM-NAB was more effective than modified FOLFIRINOX based on the result of ORR (RR: 1.43; 95% CI: 1.04–1.96). Moreover, our analysis showed a similar toxicity profile between modified FOLFIRINOX and GEM-NAB.

Conclusions

The current evidence showed that modified FOLFIRINOX and GEM-NAB were similar in survival and toxicity. Many factors should be considered for in the formulation of optimal treatment, and our meta-analysis could provide some guidance to treatment selection in the first-line setting for advanced PC.

Available only for authorised users

Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020;70(1):7–30. https://doi.org/10.3322/caac.21590.CrossRefPubMed

Ducreux M, Cuhna AS, Caramella C, Hollebecque A, Burtin P, Goere D, et al. Cancer of the pancreas: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015;26(Suppl 5):v56–68. https://doi.org/10.1093/annonc/mdv295.CrossRefPubMed

Sohal DPS, Kennedy EB, Khorana A, Copur MS, Crane CH, Garrido-Laguna I, et al. Metastatic Pancreatic Cancer: ASCO Clinical Practice Guideline Update. J Clin Oncol. 2018;36(24):2545–56. https://doi.org/10.1200/JCO.2018.78.9636.CrossRefPubMed

Von Hoff DD, Ervin T, Arena FP, Chiorean EG, Infante J, Moore M, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013;369(18):1691–703. https://doi.org/10.1056/NEJMoa1304369.CrossRef

Kang J, Hwang I, Yoo C, Kim KP, Jeong JH, Chang HM, et al. Nab-paclitaxel plus gemcitabine versus FOLFIRINOX as the first-line chemotherapy for patients with metastatic pancreatic cancer: retrospective analysis. Investig New Drugs. 2018;36(4):732–41. https://doi.org/10.1007/s10637-018-0598-5.CrossRef

Peixoto RD, Ho M, Renouf DJ, Lim HJ, Gill S, Ruan JY, et al. Eligibility of metastatic pancreatic Cancer patients for first-line palliative intent nab-paclitaxel plus gemcitabine versus FOLFIRINOX. Am J Clin Oncol. 2017;40(5):507–11. https://doi.org/10.1097/COC.0000000000000193.CrossRefPubMed

Kang H, Jo JH, Lee HS, Chung MJ, Bang S, Park SW, et al. Comparison of efficacy and safety between standard-dose and modified-dose FOLFIRINOX as a first-line treatment of pancreatic cancer. World J Gastrointest Oncol. 2018;10(11):421–30. https://doi.org/10.4251/wjgo.v10.i11.421.CrossRefPubMedPubMedCentral

Tong H, Fan Z, Liu B, Lu T. The benefits of modified FOLFIRINOX for advanced pancreatic cancer and its induced adverse events: a systematic review and meta-analysis. Sci Rep. 2018;8(1):8666. https://doi.org/10.1038/s41598-018-26811-9.CrossRefPubMedPubMedCentral

Conroy T, Desseigne F, Ychou M, Bouche O, Guimbaud R, Becouarn Y, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364(19):1817–25. https://doi.org/10.1056/NEJMoa1011923.CrossRefPubMed

10.

Kiefer C, Sturtz S, Bender R. Indirect comparisons and network meta-analyses. Dtsch Arztebl Int. 2015;112(47):803–8. https://doi.org/10.3238/arztebl.2015.0803.CrossRefPubMedPubMedCentral

11.

Kim H, Gurrin L, Ademi Z, Liew D. Overview of methods for comparing the efficacies of drugs in the absence of head-to-head clinical trial data. Br J Clin Pharmacol. 2014;77(1):116–21. https://doi.org/10.1111/bcp.12150.CrossRefPubMed

12.

Donegan S, Williamson P, D'Alessandro U, Tudur Smith C. Assessing key assumptions of network meta-analysis: a review of methods. Res Synth Methods. 2013;4(4):291–323. https://doi.org/10.1002/jrsm.1085.CrossRefPubMed

13.

Salanti G. Indirect and mixed-treatment comparison, network, or multiple-treatments meta-analysis: many names, many benefits, many concerns for the next generation evidence synthesis tool. Res Synth Methods. 2012;3(2):80–97. https://doi.org/10.1002/jrsm.1037.CrossRefPubMed

14.

White IR, Barrett JK, Jackson D, Higgins JP. Consistency and inconsistency in network meta-analysis: model estimation using multivariate meta-regression. Res Synth Methods. 2012;3(2):111–25. https://doi.org/10.1002/jrsm.1045.CrossRefPubMedPubMedCentral

15.

Chaimani A, Higgins JP, Mavridis D, Spyridonos P, Salanti G. Graphical tools for network meta-analysis in STATA. PLoS One. 2013;8(10):e76654. https://doi.org/10.1371/journal.pone.0076654.CrossRefPubMedPubMedCentral

16.

White I. MVMETA: Stata module to perform multivariate random-effects meta-analysis. Available at: https://econpapers.repec.org/software/bocbocode/s456970.htm. Accessed May 2020.

17.

White IR. Multivariate random-effects meta-regression: updates to mvmeta. Stata J. 2011;11(2):255–70. https://doi.org/10.1177/1536867X1101100206.CrossRef

18.

Dias S, Welton NJ, Caldwell DM, Ades AE. Checking consistency in mixed treatment comparison meta-analysis. Stat Med. 2010;29(7–8):932–44. https://doi.org/10.1002/sim.3767.CrossRefPubMed

19.

Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA. Cochrane handbook for systematic reviews of interventions. Available at: https://onlinelibrary.wiley.com/doi/book/10.1002/9781119536604. Accessed May 2020.

20.

Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315(7109):629–34. https://doi.org/10.1136/bmj.315.7109.629.CrossRefPubMedPubMedCentral

21.

Barrera I, Ranger J, Roofigari N, Dalfen R, Batist G, Kavan P. Treatment sequencing in MPC, insights from a 3° care center. J Clin Oncol. 2019;37(4_suppl):400. https://doi.org/10.1200/JCO.2019.37.4_suppl.400.CrossRef

22.

Chan KKW, Guo H, Cheng S, Beca JM, Redmond-Misner R, Isaranuwatchai W, et al. Real-world outcomes of FOLFIRINOX vs gemcitabine and nab-paclitaxel in advanced pancreatic cancer: a population-based propensity score-weighted analysis. Cancer Med. 2020;9(1):160–9. https://doi.org/10.1002/cam4.2705.CrossRefPubMed

23.

Cho I, Kang H, Jo J, Lee H, Chung M, Park J, et al. FOLFIRINOX versus gemcitabine plus nab-paclitaxel for treatment of metastatic pancreatic cancer: a single-center cohort study. Ann Oncol. 2018;29:v45. https://doi.org/10.1093/annonc/mdy151.160.CrossRef

24.

de Jesus VHF, Camandaroba MPG, Donadio MDS, Cabral A, Muniz TP, de Moura LL, et al. Retrospective comparison of the efficacy and the toxicity of standard and modified FOLFIRINOX regimens in patients with metastatic pancreatic adenocarcinoma. J Gastrointest Oncol. 2018;9(4):694–707. https://doi.org/10.21037/jgo.2018.04.02.CrossRefPubMedPubMedCentral

25.

Javed MA, Beyer G, Le N, Vinci A, Wong H, Palmer D, et al. Impact of intensified chemotherapy in metastatic pancreatic ductal adenocarcinoma (PDAC) in clinical routine in Europe. Pancreatology. 2019;19(1):97–104. https://doi.org/10.1016/j.pan.2018.10.003.CrossRefPubMed

26.

Kang H, Jo JH, Lee HS, Chung MJ, Bang S, Park SW, et al. Comparison of efficacy and safety between standard-dose and modified-dose FOLFIRINOX as a first-line treatment of pancreatic cancer. World Journal of Gastrointestinal Oncology. 2018;10(11):421–30. https://doi.org/10.4251/wjgo.v10.i11.421.CrossRefPubMedPubMedCentral

27.

Kang J, Hwang I, Yoo C, Kim K-P, Jeong JH, Chang H-M, et al. nab-paclitaxel plus gemcitabine versus FOLFIRINOX as the first-line chemotherapy for patients with metastatic pancreatic cancer: retrospective analysis. Investig New Drugs. 2018;36(4):732–41. https://doi.org/10.1007/s10637-018-0598-5.CrossRef

28.

Kasi A, Middinti A, Cao A, Vekaria P, Patel D, Subramaniam D, et al. FOLFIRINOX versus gemcitabine nab-paclitaxel for advanced pancreatic cancer: KU Cancer center experience. J Clin Oncol. 2017;35(15_suppl):e15744. https://doi.org/10.1200/JCO.2017.35.15_suppl.e15744.CrossRef

29.

Kim S, Signorovitch JE, Yang H, Patterson-Lomba O, Xiang CQ, Ung B, et al. Comparative effectiveness of nab-paclitaxel plus gemcitabine vs FOLFIRINOX in metastatic pancreatic Cancer: a retrospective Nationwide chart review in the United States. Adv Ther. 2018;35(10):1564–77. https://doi.org/10.1007/s12325-018-0784-z.CrossRefPubMedPubMedCentral

30.

Latenstein AEJ, Mackay TM, Creemers GJ, van Eijck CHJ, de Groot JWB, Haj Mohammad N, et al. Implementation of contemporary chemotherapy for patients with metastatic pancreatic ductal adenocarcinoma: a population-based analysis. Acta Oncol. 2020;59(6):705-12. https://doi.org/10.1080/0284186X.2020.1725241.

31.

Lee J-C, Shin DW, Yang SY, Kim MJ, Kim J, Woo SM, Lee WJ, Choi KS, Jung JH, Kang J, et al. Comparison of FOLFIRINOX and gemcitabine with nab-paclitaxel in metastatic pancreatic cancer: Using Korean Pancreatic Cancer (K-PaC) Registry. J Clin Oncol. 2019;37(15). online only.

32.

Longo Muñoz F, Castillo Trujillo O, Serrano Domingo J, Martín Huertas R, Corral De La Fuente E, San Juan A, et al. Folfirinox versus nab-paclitaxel plus gemcitabine in the first-line chemotherapy for patients with advanced pancreatic ductal adenocarcinoma: A multivariate analysis of prognostic factors in a national cohort (Comunica-TTD working group). Ann Oncol. 2019;30:aa92–3.CrossRef

33.

Muranaka T, Kuwatani M, Komatsu Y, Sawada K, Nakatsumi H, Kawamoto Y, et al. Comparison of efficacy and toxicity of FOLFIRINOX and gemcitabine with nab-paclitaxel in unresectable pancreatic cancer. Journal of Gastrointestinal Oncology. 2017;8(3):566–71. https://doi.org/10.21037/jgo.2017.02.02.CrossRefPubMedPubMedCentral

34.

Nakazawa J, Otsuka T, Shimokawa M, Koga F, Ueda Y, Otsu S, et al. A multicenter retrospective study of gemcitabine plus nabpaclitaxel or FOLFIRINOX in metastatic pancreatic cancer: NAPOLEON study. Ann Oncol. 2019;30:aa17–8.CrossRef

35.

Ohba A, Ueno H, Sakamoto Y, Kondo S, Morizane C, Okusaka T. Retrospective comparison of modified FOLFIRINOX with full-dose FOLFIRINOX for advanced pancreatic cancer: A Japanese cancer center experience. J Clin Oncol. 2018;36(4):469.

36.

Papneja N, Zaidi A, Chalchal H, Moser M, Tan K, Olson C, et al. Comparisons of outcomes of real-world patients with advanced pancreatic Cancer treated with FOLFIRINOX versus gemcitabine and nab-paclitaxel a population-based cohort study. Pancreas. 2019;48(7):920–6. https://doi.org/10.1097/MPA.0000000000001340.CrossRefPubMed

37.

Tahara J, Shimizu K, Otsuka N, Akao J, Takayama Y, Tokushige K. Gemcitabine plus nab-paclitaxel vs. FOLFIRINOX for patients with advanced pancreatic cancer. Cancer Chemother Pharmacol. 2018;82(2):245–50. https://doi.org/10.1007/s00280-018-3611-y.CrossRefPubMed

38.

Terashima T, Yamashita T, Sakai A, Ohta H, Hinoue Y, Toya D, et al. Treatment patterns and outcomes of unresectable pancreatic cancer patients in real-life practice: a region-wide analysis. Jpn J Clin Oncol. 2018;48(11):966–73. https://doi.org/10.1093/jjco/hyy132.CrossRefPubMed

39.

Vienot A, Chevalier H, Bolognini C, Gherga E, Klajer E, Meurisse A, et al. FOLFOXIRI vs FOLFIRINOX as first-line chemotherapy in patients with advanced pancreatic cancer: a population-based cohort study. World J Gastrointest Oncol. 2020;12(3):332–46. https://doi.org/10.4251/wjgo.v12.i3.332.CrossRefPubMedPubMedCentral

40.

Wang Y, Camateros P, Cheung WY. A real-world comparison of FOLFIRINOX, gemcitabine plus nab-paclitaxel, and gemcitabine in advanced pancreatic cancers. J Gastrointest Cancer. 2019;50(1):62–8. https://doi.org/10.1007/s12029-017-0028-5.CrossRefPubMed

41.

Watanabe K, Hashimoto Y, Umemoto K, Takahashi H, Sasaki M, Imaoka H, Ohno I, Mitsunaga S, Ikeda M. Clinical outcome of modified FOLFIRINOX versus gemcitabine plus nab-paclitaxel as first line chemotherapy in metastatic pancreatic cancer. J Clin Oncol. 2017;35(4):438.

42.

Williet N, Saint A, Pointet AL, Tougeron D, Pernot S, Pozet A, et al. Folfirinox versus gemcitabine/nab-paclitaxel as first-line therapy in patients with metastatic pancreatic cancer: a comparative propensity score study. Ther Adv Gastroenterol. 2019;12:1756284819878660.CrossRef

43.

Pusceddu S, Ghidini M, Torchio M, Corti F, Tomasello G, Niger M, Prinzi N, Nichetti F, Coinu A, Di Bartolomeo M, et al. Comparative Effectiveness of Gemcitabine plus Nab-Paclitaxel and FOLFIRINOX in the First-Line Setting of Metastatic Pancreatic Cancer: A Systematic Review and Meta-Analysis. Cancers (Basel). 2019;11(4):484.

44.

Ducreux M, Mitry E, Ould-Kaci M, Boige V, Seitz JF, Bugat R, et al. Randomized phase II study evaluating oxaliplatin alone, oxaliplatin combined with infusional 5-FU, and infusional 5-FU alone in advanced pancreatic carcinoma patients. Ann Oncol. 2004;15(3):467–73. https://doi.org/10.1093/annonc/mdh098.CrossRefPubMed

45.

Conroy T, Paillot B, Francois E, Bugat R, Jacob JH, Stein U, et al. Irinotecan plus oxaliplatin and leucovorin-modulated fluorouracil in advanced pancreatic cancer--a Groupe Tumeurs digestives of the federation Nationale des Centres de Lutte Contre le Cancer study. J Clin Oncol. 2005;23(6):1228–36. https://doi.org/10.1200/JCO.2005.06.050.CrossRefPubMed

46.

Gourgou-Bourgade S, Bascoul-Mollevi C, Desseigne F, Ychou M, Bouche O, Guimbaud R, et al. Impact of FOLFIRINOX compared with gemcitabine on quality of life in patients with metastatic pancreatic cancer: results from the PRODIGE 4/ACCORD 11 randomized trial. J Clin Oncol. 2013;31(1):23–9. https://doi.org/10.1200/JCO.2012.44.4869.CrossRefPubMed

47.

Burris HA 3rd, Moore MJ, Andersen J, Green MR, Rothenberg ML, Modiano MR, et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol. 1997;15(6):2403–13. https://doi.org/10.1200/JCO.1997.15.6.2403.CrossRefPubMed

48.

Souglakos J, Androulakis N, Syrigos K, Polyzos A, Ziras N, Athanasiadis A, et al. FOLFOXIRI (folinic acid, 5-fluorouracil, oxaliplatin and irinotecan) vs FOLFIRI (folinic acid, 5-fluorouracil and irinotecan) as first-line treatment in metastatic colorectal cancer (MCC): a multicentre randomised phase III trial from the Hellenic oncology research group (HORG). Br J Cancer. 2006;94(6):798–805. https://doi.org/10.1038/sj.bjc.6603011.CrossRefPubMedPubMedCentral

49.

Vivaldi C, Caparello C, Musettini G, Pasquini G, Catanese S, Fornaro L, et al. First-line treatment with FOLFOXIRI for advanced pancreatic cancer in clinical practice: Patients' outcome and analysis of prognostic factors. Int J Cancer. 2016;139(4):938–45. https://doi.org/10.1002/ijc.30125.CrossRefPubMed

50.

Gresham GK, Wells GA, Gill S, Cameron C, Jonker DJ. Chemotherapy regimens for advanced pancreatic cancer: a systematic review and network meta-analysis. BMC Cancer. 2014;14(1):471. https://doi.org/10.1186/1471-2407-14-471.CrossRefPubMedPubMedCentral

51.

Ghorani E, Wong HH, Hewitt C, Calder J, Corrie P, Basu B. Safety and efficacy of modified FOLFIRINOX for advanced pancreatic adenocarcinoma: a UK single-Centre experience. Oncology. 2015;89(5):281–7. https://doi.org/10.1159/000439171.CrossRefPubMed

52.

Stein SM, James ES, Deng Y, Cong X, Kortmansky JS, Li J, et al. Final analysis of a phase II study of modified FOLFIRINOX in locally advanced and metastatic pancreatic cancer. Br J Cancer. 2016;114(7):737–43. https://doi.org/10.1038/bjc.2016.45.CrossRefPubMed

53.

McBride A, Bonafede M, Cai Q, Princic N, Tran O, Pelletier C, et al. Comparison of treatment patterns and economic outcomes among metastatic pancreatic cancer patients initiated on nab-paclitaxel plus gemcitabine versus FOLFIRINOX. Expert Rev Clin Pharmacol. 2017;10(10):1153–60. https://doi.org/10.1080/17512433.2017.1365598.CrossRefPubMed

54.

Kim GP, Parisi MF, Patel MB, Pelletier CL, Belk KW. Comparison of treatment patterns, resource utilization, and cost of care in patients with metastatic pancreatic cancer treated with first-line nab-paclitaxel plus gemcitabine or FOLFIRINOX. Expert Rev Clin Pharmacol. 2017;10(5):559–65. https://doi.org/10.1080/17512433.2017.1302330.CrossRefPubMed

55.

Sohal DPS, Duong M, Ahmad SA, Gandhi NS, Beg MS, Wang-Gillam A, et al. Efficacy of perioperative chemotherapy for Resectable pancreatic adenocarcinoma: a phase 2 randomized clinical trial. JAMA Oncol. 2021;7(3):421–7. https://doi.org/10.1001/jamaoncol.2020.7328.CrossRefPubMed

Title: Meta-analysis and indirect treatment comparison of modified FOLFIRINOX and gemcitabine plus nab-paclitaxel as first-line chemotherapy in advanced pancreatic cancer
Authors: Jiayuan Chen
Qingling Hua
Haihong Wang
Dejun Zhang
Lei Zhao
Dandan Yu
Guoliang Pi
Tao Zhang
Zhenyu Lin
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Pancreatic Cancer
Pancreatic Cancer
Published in: BMC Cancer / Issue 1/2021
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/s12885-021-08605-x

2024 ASCO Annual Meeting Coverage

Highlights of the Day: Breast cancer – metastatic

Breast Cancer Video

In this session, Dr. Wolff provides his key takeaways from the data presented in the metastatic breast cancer oral abstract session at ASCO 2024.

Watch now

Highlights of the Day: Gynecologic cancer

Gynecologic Cancer Video

Highlights of the Day: Breast Cancer – local/regional/adjuvant

Breast Cancer Video

Neoadjuvant dual immunotherapy improves melanoma outcomes

04-06-2024 Melanoma News

» View more highlights on the ASCO 2024 congress hub page

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Image Credits

ASCO 2024 | Highlights of the Day: Breast cancer – metastatic/© 2024 American Society of Clinical Oncology, all rights reserved., ASCO 2024 | Highlights of the Day: Gynecologic Cancer/© 2024 American Society of Clinical Oncology, all rights reserved., ASCO 2024 | Highlights of the Day: Breast Cancer – local/regional/adjuvant/© 2024 American Society of Clinical Oncology, all rights reserved., Melanoma/© selvanegra / Getty Images / iStock, Antibody drug conjugated with cytotoxic payload/© Love Employee / Getty images / iStock

2024 ASCO Annual Meeting

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2021

Effect of treatment center volume on outcomes in gastroenteropancreatic neuroendocrine tumor patients

Prognostic value of SEC61G in lung adenocarcinoma: a comprehensive study based on bioinformatics and in vitro validation

Prevalence and associations of axillary web syndrome in Asian women after breast cancer surgery undergoing a community-based cancer rehabilitation program

Increasing trends in the prevalence of prior cancer in newly diagnosed lung, stomach, colorectal, breast, cervical, and corpus uterine cancer patients: a population-based study

Attention to principles of exercise training: an updated systematic review of randomized controlled trials in cancers other than breast and prostate