Abstract
Purpose
FOLFIRINOX (FFN), nab-paclitaxel plus gemcitabine (GN), and gemcitabine are three systemic therapies that provide clinically meaningful benefit to patients with unresectable pancreatic cancer (UPC). There are no clinical trials that directly compare the efficacy of all three regimens. In this study, we aim to examine and compare the real-world effectiveness of these treatments.
Methods
Patients diagnosed with UPC who initiated palliative chemotherapy from August 2014 to January 2016 at any one of six cancer centers in British Columbia were identified from the provincial pharmacy. Clinical, pathological, treatment, and outcome characteristics were compared.
Results
Two hundred twenty-five patients were included: 55% men, 68% Eastern Cooperative Oncology Group 0/1, 58% metastatic disease. Patients who received FFN were younger (p < 0.001) and in better performance status (p < 0.001). Patients treated with FFN or GN experienced significantly longer median overall survival (OS) when compared to those treated with gemcitabine (14.1 vs 10.5 vs 4.2 months, respectively, p < 0.001). Progression-free survival (PFS) was also longer among patients on FFN or GN in comparison to gemcitabine (FFN, HR 0.44, 95% CI 0.24 to 0.814, p = 0.008; GN, HR 0.30, 95% CI 0.19 to 0.47, p < 0.001). A significantly higher proportion of patients require two or more dose modifications on FFN (40%) compared to GN (14%) or gemcitabine (9%) (p < 0.001).
Conclusions
Receipt of modified FFN and GN portends a better prognosis than gemcitabine alone. In the absence of a randomized comparison of all three regimens, our population-based study reveals that the introduction of modified FFN and GN confers real-world effectiveness for UPC patients.
Similar content being viewed by others
References
American Cancer Society. Cancer Facts and Figures 2016. 2016; Available at: http://www.cancer.org/research/cancerfactsstatistics/cancerfactsfigures2016/. Accessed 30 Jul 2016.
Peixoto RD, Speers C, McGahan CE, Renouf DJ, Schaeffer DF, Kennecke HF. Prognostic factors and sites of metastasis in unresectable locally advanced pancreatic cancer. Cancer Med. 2015;4(8):1171–7. https://doi.org/10.1002/cam4.459.
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.
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.
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.
R Core Team. R. A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna. 2016; Available at: https://www.R-project.org/. Accessed 30 Jan 2016.
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.
Sohal DP, Mangu PB, Khorana AA, Shah MA, Philip PA, O’Reilly EM, et al. Metastatic pancreatic cancer: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol. 2016;34(23):2784–96. https://doi.org/10.1200/JCO.2016.67.1412.
Chan K, Shah K, Lien K, Coyle D, Lam H, Ko YJA. Bayesian meta-analysis of multiple treatment comparisons of systemic regimens for advanced pancreatic cancer. PLoS One. 2014;9(10):e108749. https://doi.org/10.1371/journal.pone.0108749.
Chllamma MK, Cook N, Dhani NC, Giby K, Dodd A, Wang L, et al. FOLFIRINOX for advanced pancreatic cancer: the Princess Margaret Cancer Centre experience. Br J Cancer. 2016;115(6):649–54. https://doi.org/10.1038/bjc.2016.222.
De Vita F, Ventriglia J, Febbraro A, Laterza MM, Fabozzi A, Savastano B, et al. NAB-paclitaxel and gemcitabine in metastatic pancreatic ductal adenocarcinoma (PDAC): from clinical trials to clinical practice. BMC Cancer. 2016;16(1):709-016-2671-9. https://doi.org/10.1186/s12885-016-2671-9.
Kim GP, Parisi M, Patel M, Belk K. Real world hospital costs associated with nab-paclitaxel plus gemcitabine (nab-P+G) and FOLFIRINOX (FFX) as first line (1L) treatment (tx) for metastatic pancreatic adenocarcinoma (MPAC). J Clin Oncol. 2016;34(15_suppl):e15741.
Marthey L, Sa-Cunha A, Blanc JF, Gauthier M, Cueff A, Francois E, et al. FOLFIRINOX for locally advanced pancreatic adenocarcinoma: results of an AGEO multicenter prospective observational cohort. Ann Surg Oncol. 2015;22(1):295–301. https://doi.org/10.1245/s10434-014-3898-9.
Moorcraft SY, Khan K, Peckitt C, Watkins D, Rao S, Cunningham D, et al. FOLFIRINOX for locally advanced or metastatic pancreatic ductal adenocarcinoma: the Royal Marsden experience. Clin Colorectal Cancer. 2014;13(4):232–8. https://doi.org/10.1016/j.clcc.2014.09.005.
Rombouts SJ, Mungroop TH, Heilmann MN, van Laarhoven HW, Busch OR, Molenaar IQ, et al. FOLFIRINOX in locally advanced and metastatic pancreatic cancer: a single centre cohort study. J Cancer. 2016;7(13):1861–6. https://doi.org/10.7150/jca.16279.
Suker M, Beumer BR, Sadot E, Marthey L, Faris JE, Mellon EA, et al. FOLFIRINOX for locally advanced pancreatic cancer: a systematic review and patient-level meta-analysis. Lancet Oncol. 2016;17(6):801–10. https://doi.org/10.1016/S1470-2045(16)00172-8.
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;14:471. 2407–14-471
Tehfe M, Dowden S, Kennecke H, El-Maraghi R, Lesperance B, Couture F, et al. Nab-paclitaxel plus gemcitabine versus gemcitabine in patients with metastatic pancreatic adenocarcinoma: Canadian subgroup analysis of the phase 3 MPACT trial. Adv Ther. 2016;33(5):747–59. https://doi.org/10.1007/s12325-016-0327-4.
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.
Conroy T, Bachet JB, Ayav A, Huguet F, Lambert A, Caramella C, et al. Current standards and new innovative approaches for treatment of pancreatic cancer. Eur J Cancer. 2016;57:10–22. https://doi.org/10.1016/j.ejca.2015.12.026.
Goldstein D, Von Hoff DD, Moore M, Greeno E, Tortora G, Ramanathan RK, et al. Development of peripheral neuropathy and its association with survival during treatment with nab-paclitaxel plus gemcitabine for patients with metastatic adenocarcinoma of the pancreas: a subset analysis from a randomised phase III trial (MPACT). Eur J Cancer. 2016;52:85–91. https://doi.org/10.1016/j.ejca.2015.10.017.
Park SB, Lin CS, Krishnan AV, Goldstein D, Friedlander ML, Kiernan MC. Long-term neuropathy after oxaliplatin treatment: challenging the dictum of reversibility. Oncologist. 2011;16(5):708–16. https://doi.org/10.1634/theoncologist.2010-0248.
Portal A, Pernot S, Tougeron D, Arbaud C, Bidault AT, de la Fouchardiere C, et al. Nab-paclitaxel plus gemcitabine for metastatic pancreatic adenocarcinoma after Folfirinox failure: an AGEO prospective multicentre cohort. Br J Cancer. 2015;113(7):989–95. https://doi.org/10.1038/bjc.2015.328.
Gill S, Ko YJ, Cripps C, Beaudoin A, Dhesy-Thind S, Zulfiqar M, et al. PANCREOX: a randomized phase III study of 5-fluorouracil/leucovorin with or without oxaliplatin for second-line advanced pancreatic cancer in patients who have received gemcitabine-based chemotherapy. J Clin Oncol. 2016;34(32):3914–20. https://doi.org/10.1200/JCO.2016.68.5776.
Vogel A, Ciardiello F, Hubner RA, Blanc JF, Carrato A, Yang Y, et al. Post-gemcitabine therapy for patients with advanced pancreatic cancer—a comparative review of randomized trials evaluating oxaliplatin- and/or irinotecan-containing regimens. Cancer Treat Rev. 2016;50:142–7. https://doi.org/10.1016/j.ctrv.2016.09.001.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Ethics approval was obtained from the Institutional Review Board prior to the conduct of the study.
Conflict of Interest
The authors declare that they have no conflict of interest.
Rights and permissions
About this article
Cite this article
Wang, Y., Camateros, P. & Cheung, W.Y. A Real-World Comparison of FOLFIRINOX, Gemcitabine Plus nab-Paclitaxel, and Gemcitabine in Advanced Pancreatic Cancers. J Gastrointest Canc 50, 62–68 (2019). https://doi.org/10.1007/s12029-017-0028-5
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12029-017-0028-5