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A pilot study of first-line olaratumab, doxorubicin and ifosfamide in patients with metastatic soft tissue sarcoma

  • Olga Vornicova
  • Nissim Haim
  • Gil Bar-SelaEmail author
Short Communication
  • 1 Downloads

Abstract

Introduction

Olaratumab (O) is a monoclonal antibody that specifically binds PDGFRα. The addition of O to doxorubicin (D) has been approved by the regulatory authorities for metastatic soft tissue sarcoma (MSTS). Since the combination of D + ifosfamide (I) is commonly used in MSTS and is associated with a higher response rate than D alone, it seems reasonable to combine O with the combination of D + I (ODI). We report our preliminary experience with O + D+I in MSTS.

Methods

Between 01/01/2015 and 30/05/2018, 15 patients (pts) with MSTS were treated with ODI as first-line therapy. The treatment protocol consisted of IV D 50 mg/m2 and I 5000 mg/m2, day 1 (3 pts), or D 37.5 mg/m2 and I 3000 mg/m2 days 1–2 (12 pts). O (15 mg/kg) was given IV on days 1, 8, and cycles were repeated every 21 days.

Results

With a median follow up of 16 months, 63 cycles of ODI were given. Objective response was achieved in 4 pts (27%) (CR in 3, PR in 1); 5 pts (33%) remained with stable disease for ≥ 5 mo. Median overall survival was 22 months. Major hematological toxicities (grade 3–4) included: neutropenia—7 pts (47%), and neutropenic fever—3 pts (20%). Non-hematological toxicities included grade 3 diarrheas in 2 pts (13%) after the second cycle. There was no treatment-related mortality.

Conclusion

According to our preliminary experience, adding olaratumab to doxorubicin and ifosfamide is active and its safety profile is comparable to that of doxorubicin and ifosfamide alone in MSTS.

Keywords

Olaratumab Doxorubicin Ifosfamide Soft tissue sarcoma Safety 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Singer S, Demetri GD, Baldini EH, Fletcher CD (2000) Management of soft-tissue sarcomas: an overview and update. Lancet Oncol 1:75–85CrossRefGoogle Scholar
  2. 2.
    Ng F, Boucher S, Koh S, Sastry KS, Chase L, Lakshmipathy U, Choong C, Yang Z, Vemuri MC, Rao MS, Tanavde V (2008) PDGF, TGF-beta, and FGF signaling is important for differentiation and growth of mesenchymal stem cells (MSCs): transcriptional profiling can identify markers and signaling pathways important in differentiation of MSCs into adipogenic, chondrogenic, and osteogenic lineages. Blood 112:295–307.  https://doi.org/10.1182/blood-2007-07-103697 CrossRefGoogle Scholar
  3. 3.
    Chen CY, Liu SH, Chen CY, Chen PC, Chen CP (2015) Human placenta-derived multipotent mesenchymal stromal cells involved in placental angiogenesis via the PDGF-BB and STAT3 pathways. Biol Reprod 93:103.  https://doi.org/10.1095/biolreprod.115.131250 CrossRefGoogle Scholar
  4. 4.
    Ostman A, Heldin CH (2001) Involvement of platelet-derived growth factor in disease: development of specific antagonists. Adv Cancer Res 80:1–38CrossRefGoogle Scholar
  5. 5.
    Loizos N, Xu Y, Huber J et al (2005) Targeting the platelet-derived growth factor receptor alpha with a neutralizing human monoclonal antibody inhibits the growth of tumour xenografts: implications as a potential therapeutic target. Mol Cancer Ther 4:369–379Google Scholar
  6. 6.
    Tap WD, Jones RL, Van Tine BA, Chmielowski B (2016) Olaratumab and doxorubicin versus doxorubicin alone for treatment of soft-tissue sarcoma: an open-label phase 1b and randomised phase 2 trial. Lancet 30(388):488–497.  https://doi.org/10.1016/S0140-6736(16)30587-6 CrossRefGoogle Scholar
  7. 7.
    Leyvraz S, Zweifel M, Jundt G, Swiss Group for Clinical Cancer Research et al (2006) Long-term results of a multicenter SAKK trial on high-dose ifosfamide and doxorubicin in advanced or metastatic gynecologic sarcomas. Ann Oncol 17:646–651CrossRefGoogle Scholar
  8. 8.
    Judson I, Verweij J, Gelderblom H, Hartmann JT (2014) Doxorubicin alone versus intensified doxorubicin plus ifosfamide for first-line treatment of advanced or metastatic soft-tissue sarcoma: a randomised controlled phase 3 trial. Lancet Oncol. 15:415–423.  https://doi.org/10.1016/S1470-2045(14)70063-4 CrossRefGoogle Scholar
  9. 9.
    Ryan CW, Merimsky O, Agulnik M et al (2016) PICASSO III: a phase III, placebo-controlled study of doxorubicin with or without palifosfamide in patients with metastatic soft tissue sarcoma. J Clin Oncol 34:3898–3905.  https://doi.org/10.1200/JCO.2016.67.6684 CrossRefGoogle Scholar
  10. 10.
    Tap WD, et al (2019) ANNOUNCE: A randomized, placebo (PBO)-controlled, double-blind, phase (Ph) III trial of doxorubicin (dox) + olaratumab versus dox + PBO in patients (pts) with advanced soft tissue sarcomas (STS). Abstract LBA3. ASCO Meeting, Chicago USAGoogle Scholar
  11. 11.
    Le Cesne A, Judson I, Crowther D et al (2000) Randomized phase III study comparing conventional-dose doxorubicin plus ifosfamide versus high-dose doxorubicin plus ifosfamide plus recombinant human granulocyte-macrophage colony-stimulating factor in advanced soft tissue sarcomas: a trial of the European Organization for Research and Treatment of Cancer/Soft Tissue and Bone Sarcoma Group. J Clin Oncol 18:2676–2684CrossRefGoogle Scholar
  12. 12.

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Cancer CenterEmek Medical CenterAfulaIsrael
  2. 2.Faculty of MedicineTechnion-Israel Institute of TechnologyHaifaIsrael
  3. 3.Division of OncologyRambam Health Care CampusHaifaIsrael

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