Impact of G-CSF Prophylaxis on Chemotherapy Dose-Intensity, Link Between Dose-Intensity and Survival in Patients with Metastatic Pancreatic Adenocarcinoma

Clémence Canton, Olayidé Boussari, Mathieu Boulin, Karine Le Malicot, Julien Taieb, Laetitia Dahan, Anthony Lopez, Come Lepage, Jean-Baptiste Bachet, Clémence Canton, Olayidé Boussari, Mathieu Boulin, Karine Le Malicot, Julien Taieb, Laetitia Dahan, Anthony Lopez, Come Lepage, Jean-Baptiste Bachet

Abstract

Background: In metastatic pancreatic adenocarcinoma, few data are available on the use of granulocyte-colony stimulating factor (G-CSF) prophylaxis and its impact on dose-intensity (DI), or the link between DI and progression-free survival (PFS). This study assessed the impact of G-CSF prophylaxis on the DI received by patients and the relationship between full DI and PFS according to chemotherapy regimens.

Patients and methods: Patients from three first-line randomized phase II clinical trials were included in this retrospective cohort. G-CSF prophylaxis groups were identified and balanced according to baseline characteristics using a propensity score. Patients were classified into 2 treatment groups (FOLFIRINOX vs FOLFIRI/nab-paclitaxel (NAB)). DI was a binary variable (full/reduced). Adverse events were defined using NCI-CTCAE v4.0.

Results: Of the 498 patients, 154 (31%) were in "prophylaxis" group; 179 (36%) were treated by FOLFIRINOX and 319 (64%) by FOLFIRI/NAB. In FOLFIRINOX group, G-CSF prophylaxis was significantly associated with a higher rate of full DI (OR, 5.07; 95% CI, 1.52-16.90; P < .01) while in FOLFIRI/NAB group, it was significantly associated with a lower rate of full DI (OR, 0.23; 95% CI, 0.06-0.83; P = .03). Full DI was associated with a non-significant increase in PFS (FOLFIRINOX group: HR 0.83; 95% CI, 0.59-1.16; P = .27; FOLFIRI/NAB group: HR 0.84; 95% CI, 0.63-1.11; P = .22).

Conclusion: Granulocyte-colony stimulating factor prophylaxis was associated with a higher rate of full DI with FOLFIRINOX. Full DI was associated with a non-significant increase in PFS. These results need to be confirmed prospectively.

Keywords: dose-intensity; granulocyte-colony stimulating factor prophylaxis; metastatic pancreatic adenocarcinoma; progression-free survival; propensity score.

© The Author(s) 2022. Published by Oxford University Press.

Figures

Figure 1.
Figure 1.
Study flowchart patients’ classification by prophylaxis group. PP, primary prophylaxis; ØP, no prophylaxis; SP, secondary prophylaxis; FN, febrile neutropenia.
Figure 2.
Figure 2.
Kaplan-Meier estimates of PFS according to prophylaxis group. Kaplan-Meier curve for PFS. PP, primary prophylaxis; ØP, no prophylaxis; SP, secondary prophylaxis.

References

    1. Burris HA, Moore MJ, Andersen J, 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;15:2403-2413. 10.1200/JCO.1997.15.6.2403
    1. Conroy T, Desseigne F, Ychou M, et al. . FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364:1817-1825. 10.1056/NEJMoa1011923
    1. Von Hoff DD, Ervin T, Arena FP, et al. . Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013;369:1691-1703. 10.1056/NEJMoa1304369
    1. National Cancer Institute Cancer Therapy Evaluation Program. Common Terminology Criteria for Adverse Events (CTCAE). Available at . Accessed March 5, 2021.
    1. Bosly A, Bron D, Van Hoof A, et al. . Achievement of optimal average relative dose intensity and correlation with survival in diffuse large B-cell lymphoma patients treated with CHOP. Ann Hematol. 2008;87:277-283. 10.1007/s00277-007-0399-y
    1. Chirivella I, Bermejo B, Insa A, et al. . Optimal delivery of anthracycline-based chemotherapy in the adjuvant setting improves outcome of breast cancer patients. Breast Cancer Res Treat. 2009;114:479-484. 10.1007/s10549-008-0018-1
    1. Radosavljevic D, Golubicic I, Gavrilovic D, et al. . Do the time to chemotherapy response and the dose intensity have an impact on patient outcome in advanced non-small cell lung cancer? J BUON. 2009;14:203-209.
    1. Sarosy GA, Hussain MM, Seiden MV, et al. . Ten-year follow-up of a phase 2 study of dose-intense paclitaxel with cisplatin and cyclophosphamide as initial therapy for poor-prognosis, advanced-stage epithelial ovarian cancer. Cancer 2010;116:1476-1484. 10.1002/cncr.24861
    1. Green MD, Koelbl H, Baselga J, et al. . A randomized double-blind multicenter phase III study of fixed-dose single-administration pegfilgrastim versus daily filgrastim in patients receiving myelosuppressive chemotherapy. Ann Oncol. 2003;14:29-35. 10.1093/annonc/mdg019
    1. Gisselbrecht C, Haioun C, Lepage E, et al. . Placebo-controlled phase III study of lenograstim (glycosylated recombinant human granulocyte colony-stimulating factor) in aggressive non-Hodgkin’s lymphoma: factors influencing chemotherapy administration. Groupe d’Etude des Lymphomes de l’Adulte. Leuk Lymphoma. 1997;25:289-300. 10.3109/10428199709114168
    1. Aapro MS, Cameron DA, Pettengell R, et al. . EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphomas and solid tumours. Eur J Cancer. 2006;42:2433-2453. 10.1016/j.ejca.2006.05.002
    1. Aapro MS, Bohlius J, Cameron DA, et al. . 2010 update of EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphoproliferative disorders and solid tumours. Eur J Cancer. 2011;47:8-32. 10.1016/j.ejca.2010.10.013
    1. Klastersky J, de Naurois J, Rolston K, et al. . Management of febrile neutropaenia: ESMO clinical practice guidelines. Ann Oncol. 2016;27:v111-v118. 10.1093/annonc/mdw325
    1. Smith TJ, Bohlke K, Lyman GH, et al. . Recommendations for the use of WBC growth factors: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol. 2015;33:3199-3212. 10.1200/JCO.2015.62.3488
    1. Chen P, Lei J, Wu Y, et al. . Pegylated G-CSF combined with mFOLFIRINOX for advanced pancreatic cancer patients. Intern Med. 2020;59:877. 10.2169/internalmedicine.3790-19
    1. Yamao K, Takenaka M, Yoshikawa T, et al. . Clinical safety and efficacy of secondary prophylactic pegylated G-CSF in advanced pancreatic cancer patients treated with mFOLFIRINOX: a single-center retrospective study. Intern Med. 2019;58:1993-2002. 10.2169/internalmedicine.2234-18
    1. Ninomiya R, Nakazawa A, Miyata Y, et al. . Primary prophylactic administration of pegfilgrastim in FOLFIRINOX therapy for locally advanced pancreatic carcinoma. Gan To Kagaku Ryoho 2016;43:1678-1680.
    1. Conroy T, Hammel P, Hebbar M, et al. . FOLFIRINOX or gemcitabine as adjuvant therapy for pancreatic cancer. N Engl J Med. 2018;379:2395-2406. 10.1056/NEJMoa1809775
    1. Dahan L, Williet N, Le Malicot K, et al. . Randomized phase II trial evaluating two sequential treatments in first line of metastatic pancreatic cancer: results of the PANOPTIMOX-PRODIGE 35 trial. J Clin Oncol. 2021;39:3242-3250.
    1. Rinaldi Y, Pointet A-L, Khemissa Akouz F, et al. . Gemcitabine plus nab-paclitaxel until progression or alternating with FOLFIRI.3, as first-line treatment for patients with metastatic pancreatic adenocarcinoma: The Federation Francophone de Cancérologie Digestive-PRODIGE 37 randomised phase II study (FIRGEMAX). Eur J Cancer. 2020;136:25-34. 10.1016/j.ejca.2020.05.018
    1. Bachet J-B, Hammel P, Desramé J, et al. . Nab-paclitaxel plus either gemcitabine or simplified leucovorin and fluorouracil as first-line therapy for metastatic pancreatic adenocarcinoma (AFUGEM GERCOR): a non-comparative, multicentre, open-label, randomised phase 2 trial. Lancet Gastroenterol Hepatol 2017;2:337-346. 10.1016/S2468-1253(17)30046-8
    1. Rosenbaum PR, Rubin DB.. The central role of the propensity score in observational studies for causal effects. Biometrika 1983;70:41-55. 10.1093/biomet/70.1.41
    1. D’Agostino RB. Propensity score methods for bias reduction in the comparison of a treatment to a non-randomized control group. Stat Med. 1998;17:2265-2281. 10.1002/(sici)1097-0258(19981015)17:19<2265::aid-sim918>;2-b
    1. Bates D, Kliegl R, Vasishth S, et al. . Parsimonious mixed models. arXiv: 1506.04967v2 [] 2018. Available at: .
    1. Austin PC. A tutorial on multilevel survival analysis: methods, models and applications. Int Stat Rev. 2017;85:185-203. 10.1111/insr.12214
    1. Pettengell R, Gurney H, Radford JA, et al. . Granulocyte colony-stimulating factor to prevent dose-limiting neutropenia in non-Hodgkin’s lymphoma: a randomized controlled trial. Blood 1992;80:1430-1436.
    1. Leonard RCF, Mansi JL, Keerie C, et al. . A randomised trial of secondary prophylaxis using granulocyte colony-stimulating factor (‘SPROG’ trial) for maintaining dose intensity of standard adjuvant chemotherapy for breast cancer by the Anglo-Celtic Cooperative Group and NCRN. Ann Oncol. 2015;26:2437-2441. 10.1093/annonc/mdv389
    1. Sternberg CN, Mulder PHM de, Schornagel JHet al. . Randomized phase III trial of high-dose-intensity methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) chemotherapy and recombinant human granulocyte colony-stimulating factor versus classic MVAC in advanced urothelial tract tumors: European Organization for Research and Treatment of Cancer Protocol No. 30924. J Clin Oncol 2016. 10.1200/JCO.2001.19.10.2638
    1. Bohlius J, Herbst C, Reiser M, et al. . Granulopoiesis-stimulating factors to prevent adverse effects in the treatment of malignant lymphoma. Cochrane Database Syst Rev. 2008;(4):CD003189. 10.1002/14651858.CD003189.pub4
    1. Lal A, Bhurgri Y, Rizvi N, et al. . Factors influencing in-hospital length of stay and mortality in cancer patients suffering from febrile neutropenia. Asian Pac J Cancer Prev. 2008;9:303-308.
    1. Lyman GH, Dale DC, Culakova E, et al. . The impact of the granulocyte colony-stimulating factor on chemotherapy dose intensity and cancer survival: a systematic review and meta-analysis of randomized controlled trials. Ann Oncol. 2013;24:2475-2484. 10.1093/annonc/mdt226
    1. Kawahira M, Yokota T, Hamauchi S, et al. . Primary prophylactic granulocyte colony-stimulating factor according to ASCO guidelines has no preventive effect on febrile neutropenia in patients treated with docetaxel, cisplatin, and 5-fluorouracil chemotherapy. Int J Clin Oncol. 2018;23:1189-1195. 10.1007/s10147-018-1306-3
    1. Pinter T, Klippel Z, Cesas A, et al. . A phase III, randomized, double-blind, placebo-controlled trial of pegfilgrastim in patients receiving first-line FOLFOX/bevacizumab or FOLFIRI/bevacizumab for locally advanced or metastatic colorectal cancer: final results of the pegfilgrastim and anti-VEGF evaluation study (PAVES). Clin Colorectal Cancer. 2017;16:103-114.e3. 10.1016/j.clcc.2016.08.008
    1. Smith TJ, Khatcheressian J, Lyman GH, et al. . 2006 update of recommendations for the use of white blood cell growth factors: an evidence-based clinical practice guideline. J Clin Oncol. 2006;24:3187-3205. 10.1200/JCO.2006.06.4451
    1. Base de données publique des médicaments. Available at . Accessed May 24, 2020.
    1. Luo G, Guo M, Liu Z, et al. . Blood neutrophil-lymphocyte ratio predicts survival in patients with advanced pancreatic cancer treated with chemotherapy. Ann Surg Oncol. 2015;22:670-676. 10.1245/s10434-014-4021-y
    1. Guo J, Wu M, Guo L, et al. . Pretreatment blood neutrophil/lymphocyte ratio is associated with metastasis and predicts survival in patients with pancreatic cancer. Bull Cancer. 2018;105:146-154. 10.1016/j.bulcan.2017.10.028

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