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Supportive Care in Cancer

, Volume 24, Issue 1, pp 267–273 | Cite as

Incidence of bone pain in patients with breast cancer treated with lipegfilgrastim or pegfilgrastim: an integrated analysis from phase II and III studies

  • I. M. BondarenkoEmail author
  • P. Bias
  • A. Buchner
Original Article

Abstract

Purpose

Lipegfilgrastim is a once-per-cycle, fixed-dose, glycoPEGylated recombinant granulocyte colony-stimulating factor (G-CSF) recently approved in Europe to reduce the duration of chemotherapy-induced neutropenia and incidence of febrile neutropenia in patients with cancer receiving chemotherapy. Bone pain-related (BPR) adverse events are commonly associated with G-CSF therapy. This post hoc analysis examined BPR treatment-emergent adverse events (TEAEs) in two comparative studies of lipegfilgrastim or pegfilgrastim in patients receiving chemotherapy.

Methods

A post hoc analysis was conducted using integrated data from two double-blind randomized studies in patients with breast cancer receiving docetaxel and doxorubicin and treated prophylactically with subcutaneous lipegfilgrastim 6 mg or pegfilgrastim 6 mg once per cycle. BPR TEAEs were defined as arthralgia, back pain, bone pain, musculoskeletal chest pain, musculoskeletal discomfort, musculoskeletal pain, myalgia, neck pain, noncardiac chest pain, and pain in extremity. Relationship of BPR TEAEs to study treatment or chemotherapy was also reported by the investigators.

Results

The analysis included 306 patients (lipegfilgrastim: n = 151; pegfilgrastim: n = 155). The proportion of patients experiencing BPR TEAEs was similar with lipegfilgrastim and pegfilgrastim (25.2 vs 21.9 %, respectively), as was the proportion of patients experiencing BPR treatment-emergent adverse drug reactions (TEADRs) (18.5 vs 16.8 %, respectively). No BPR TEADRs were serious, and none led to discontinuation.

Conclusions

Nonsevere BPR TEAEs and TEADRs were observed in patients with breast cancer receiving chemotherapy and G-CSF; rates of BPR events were similar between lipegfilgrastim and pegfilgrastim. The similar BPR safety profile of lipegfilgrastim and pegfilgrastim provides support for use in patients with breast cancer receiving chemotherapy.

Keywords

Lipegfilgrastim Pegfilgrastim Bone pain Drug-related side effect Docetaxel Doxorubicin 

Notes

Acknowledgments

This post hoc analysis was sponsored by Teva Branded Pharmaceutical Products R&D, Inc. Medical writing assistance was provided by Lisa Feder, PhD, of Peloton Advantage and was funded by Teva Branded Pharmaceutical Products R&D, Inc. Teva provided a full review of the article.

Conflict of interest

I.M. Bondarenko is a stock shareholder of Merckle GmbH. P. Bias is an employee of Teva Ratiopharm. A. Buchner is an employee and stock shareholder of Merckle GmbH.

References

  1. 1.
    Cooper KL, Madan J, Whyte S, Stevenson MD, Akehurst RL (2011) Granulocyte colony-stimulating factors for febrile neutropenia prophylaxis following chemotherapy: systematic review and meta-analysis. BMC Cancer 11:404. doi: 10.1186/1471-2407-11-404 PubMedCentralCrossRefPubMedGoogle Scholar
  2. 2.
    Crawford J, Caserta C, Roila F (2010) Hematopoietic growth factors: ESMO Clinical Practice Guidelines for the applications. Ann Oncol 21(suppl 5):v248–v251. doi: 10.1093/annonc/mdq195 CrossRefPubMedGoogle Scholar
  3. 3.
    Aapro MS, Bohlius J, Cameron DA et al (2011) 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 47:8–32. doi: 10.1016/j.ejca.2010.10.013 CrossRefPubMedGoogle Scholar
  4. 4.
    (2014) NCCN Clinical Practice Guidelines in Oncology. Myeloid growth factors v.2.2014. National Comprehensive Cancer Network. www.nccn.org/professionals/physician_gls/f_guidelines.asp. Accessed 23 January 2015
  5. 5.
    Smith TJ, Khatcheressian J, Lyman GH et al (2006) 2006 update of recommendations for the use of white blood cell growth factors: an evidence-based clinical practice guideline. J Clin Oncol 24:3187–3205. doi: 10.1200/JCO.2006.06.4451 CrossRefPubMedGoogle Scholar
  6. 6.
    Lonquex: summary of product characteristics (2013) European Medicines Agency, London, UKGoogle Scholar
  7. 7.
    Bondarenko I, Gladkov OA, Elsaesser R, Buchner A, Bias P (2013) Efficacy and safety of lipegfilgrastim versus pegfilgrastim: a randomized, multicenter, active-control phase 3 trial in patients with breast cancer receiving doxorubicin/docetaxel chemotherapy. BMC Cancer 13:386–398. doi: 10.1186/1471-2407-13-386 PubMedCentralCrossRefPubMedGoogle Scholar
  8. 8.
    Tigue CC, McKoy JM, Evens AM, Trifilio SM, Tallman MS, Bennett CL (2007) Granulocyte-colony stimulating factor administration to healthy individuals and persons with chronic neutropenia or cancer: an overview of safety considerations from the Research on Adverse Drug Events and Reports project. Bone Marrow Transplant 40:185–192. doi: 10.1038/sj.bmt.1705722 CrossRefPubMedGoogle Scholar
  9. 9.
    Lambertini M, Del Mastro L, Bellodi A, Pronzato P (2013) The five “Ws” for bone pain due to the administration of granulocyte-colony stimulating factors (G-CSFs). Crit Rev Oncol Hematol 89:112–128. doi: 10.1016/j.critrevonc.2013.08.006 CrossRefPubMedGoogle Scholar
  10. 10.
    Holmes FA, Jones SE, O’Shaughnessy J et al (2002) Comparable efficacy and safety profiles of once-per-cycle pegfilgrastim and daily injection filgrastim in chemotherapy-induced neutropenia: a multicenter dose-finding study in women with breast cancer. Ann Oncol 13:903–909CrossRefPubMedGoogle Scholar
  11. 11.
    Holmes FA, O’Shaughnessy JA, Vukelja S et al (2002) Blinded, randomized, multicenter study to evaluate single administration pegfilgrastim once per cycle versus daily filgrastim as an adjunct to chemotherapy in patients with high-risk stage II or stage III/IV breast cancer. J Clin Oncol 20:727–731CrossRefPubMedGoogle Scholar
  12. 12.
    Green MD, Koelbl H, Baselga J et al (2003) A randomized double-blind multicenter phase III study of fixed-dose single-administration pegfilgrastim versus daily filgrastim in patients receiving myelosuppressive chemotherapy. Ann Oncol 14:29–35CrossRefPubMedGoogle Scholar
  13. 13.
    Kirshner JJ, Heckler CE, Janelsins MC et al (2012) Prevention of pegfilgrastim-induced bone pain: a phase III double-blind placebo-controlled randomized clinical trial of the University of Rochester Cancer Center Clinical Community Oncology Program Research Base. J Clin Oncol 30:1974–1979. doi: 10.1200/JCO.2011.37.8364 PubMedCentralCrossRefPubMedGoogle Scholar
  14. 14.
    Vogel CL, Wojtukiewicz MZ, Carroll RR et al (2005) First and subsequent cycle use of pegfilgrastim prevents febrile neutropenia in patients with breast cancer: a multicenter, double-blind, placebo-controlled phase III study. J Clin Oncol 23:1178–1184. doi: 10.1200/JCO.2005.09.102 CrossRefPubMedGoogle Scholar
  15. 15.
    Kubista E, Glaspy J, Holmes FA, Green MD, Hackett J, Neumann T (2003) Bone pain associated with once-per-cycle pegfilgrastim is similar to daily filgrastim in patients with breast cancer. Clin Breast Cancer 3:391–398CrossRefPubMedGoogle Scholar
  16. 16.
    Kirshner JJ, Hickok J, Hofman M (2007) Pegfilgrastim-induced bond pain: incidence, risk factors, and management in a community practice. Community Oncol 4:455–459CrossRefGoogle Scholar
  17. 17.
    Buchner A, Bias P, Kaufmann M, Mueller U (2012) A randomized, double-blind, active control, multicenter, dose finding study of lipegfilgrastim in breast cancer patients receiving myelosuppressive therapy [abstract 1004]. Support Care Cancer 20:S240Google Scholar
  18. 18.
    Buchner A, Elsasser R, Bias P (2014) A randomized, double-blind, active control, multicenter, dose-finding study of lipegfilgrastim (XM22) in breast cancer patients receiving myelosuppressive therapy. Breast Cancer Res Treat 148:107–116. doi: 10.1007/s10549-014-3120-6 PubMedCentralCrossRefPubMedGoogle Scholar
  19. 19.
    Alba E, Martin M, Ramos M et al (2004) Multicenter randomized trial comparing sequential with concomitant administration of doxorubicin and docetaxel as first-line treatment of metastatic breast cancer: a Spanish Breast Cancer Research Group (GEICAM-9903) phase III study. J Clin Oncol 22:2587–2593. doi: 10.1200/JCO.2004.08.125 CrossRefPubMedGoogle Scholar
  20. 20.
    Nabholtz JM, Falkson C, Campos D et al (2003) Docetaxel and doxorubicin compared with doxorubicin and cyclophosphamide as first-line chemotherapy for metastatic breast cancer: results of a randomized, multicenter, phase III trial. J Clin Oncol 21:968–975CrossRefPubMedGoogle Scholar
  21. 21.
    Waller CF, Semiglazov VF, Tjulandin S, Bentsion D, Chan S, Challand R (2010) A phase III randomized equivalence study of biosimilar filgrastim versus Amgen filgrastim in patients receiving myelosuppressive chemotherapy for breast cancer. Onkologie 33:504–511. doi: 10.1159/000319693 CrossRefPubMedGoogle Scholar
  22. 22.
    Pinto L, Liu Z, Doan Q, Bernal M, Dubois R, Lyman G (2007) Comparison of pegfilgrastim with filgrastim on febrile neutropenia, grade IV neutropenia and bone pain: a meta-analysis of randomized controlled trials. Curr Med Res Opin 23:2283–2295. doi: 10.1185/030079907X219599 CrossRefPubMedGoogle Scholar
  23. 23.
    Andre N, El Kababri M, Bertrand P et al (2007) Safety and efficacy of pegfilgrastim in children with cancer receiving myelosuppressive chemotherapy. Anticancer Drugs 18:277–281. doi: 10.1097/CAD.0b013e328011a532 CrossRefPubMedGoogle Scholar
  24. 24.
    Almenar D, Mayans J, Juan O et al (2009) Pegfilgrastim and daily granulocyte colony-stimulating factor: patterns of use and neutropenia-related outcomes in cancer patients in Spain—results of the LEARN Study. Eur J Cancer Care 18:280–286. doi: 10.1111/j.1365-2354.2008.00959.x CrossRefGoogle Scholar
  25. 25.
    Kuderer NM, Dale DC, Crawford J, Lyman GH (2007) Impact of primary prophylaxis with granulocyte colony-stimulating factor on febrile neutropenia and mortality in adult cancer patients receiving chemotherapy: a systematic review. J Clin Oncol 25:3158–3167. doi: 10.1200/JCO.2006.08.8823 CrossRefPubMedGoogle Scholar
  26. 26.
    Volovat C, Bondarenko IM, Gladkov OA, et al (2015) Phase III, randomized, double-blind, placebo-controlled, multicenter study of lipegfilgrastim in patients with non–small cell lung cancer receiving myelosuppressive therapy. SpringerPlus: in pressGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  1. 1.Dnipropetrovsk State Medical AcademyDnipropetrovskUkraine
  2. 2.Teva RatiopharmUlmGermany
  3. 3.Merckle GmbHUlmGermany

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