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Eltrombopag for thrombocytopenia in patients with advanced solid tumors receiving gemcitabine-based chemotherapy: a randomized, placebo-controlled phase 2 study

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Abstract

In this phase 2 study, patients with solid tumors receiving gemcitabine monotherapy or gemcitabine plus cisplatin/carboplatin were randomized 2:1 to eltrombopag 100 mg (n = 52) or placebo (n = 23) for 5 days before and after chemotherapy was started. The primary endpoint was prechemotherapy (Day 1) platelet count across ≤6 cycles. Prechemotherapy platelet counts were numerically higher with eltrombopag than placebo. Frequencies of grades 3/4 thrombocytopenia were lower with eltrombopag in both the combination therapy (77 vs. 100%) and monotherapy (36 vs. 42%) groups. Proportionately fewer eltrombopag-treated patients had platelet counts <100 × 109/L at nadir. Among patients receiving combination chemotherapy, mean time to recovery from platelet nadir was 8 days with eltrombopag vs. 15 days with placebo. Eltrombopag-treated patients had fewer dose delays/reductions or missed doses due to thrombocytopenia in both the combination therapy (77 vs. 91%) and monotherapy (62 vs. 83%) groups. Adverse events and serious adverse events were less frequent with eltrombopag in both chemotherapy groups, with reduced rates of anemia, neutropenia, and thrombocytopenia in patients receiving combination chemotherapy. In conclusion, eltrombopag treatment shortened the time to recovery from platelet nadir in patients treated with gemcitabine-based chemotherapy and reduced dose delays/reductions due to thrombocytopenia.

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Acknowledgements

Funding for this study (NCT01147809 available from https://clinicaltrials.gov/ct2/show/NCT01147809) was provided by GlaxoSmithKline; however, as of March 2, 2015, eltrombopag is an asset of Novartis AG. We thank Vassilios Aslanis, PharmD, of Novartis Pharmaceuticals Corporation, for his critical review of the manuscript and the pharmacology data. We also thank the patients and principal investigators and their institutions for their contributions to the study. All listed authors meet the criteria for authorship set forth by the International Committee for Medical Journal Editors. Editorial support (assembling tables and figures, collating author comments, copyediting, fact checking, and referencing) and graphic services were provided by Elizabeth Rosenberg, PhD, and Nancy E. Price, PhD, of AOI Communications, L.P., and were funded by Novartis Pharmaceuticals Corporation.

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Authors and Affiliations

  1. Dana Farber Cancer Institute, 450 Brookline Avenue, Boston, MA, 02215, USA

    Eric S. Winer

  2. Brown University Oncology Research Group, Providence, RI, USA

    Howard Safran

  3. Komed Branch Medical Center, Konin, Poland

    Boguslawa Karaszewska

  4. Department of Medical Oncology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany

    Sebastian Bauer

  5. Harbin Clinic, Rome, GA, USA

    Dilawar Khan

  6. Onkozentrum Dresden, Dresden, Germany

    Steffen Doerfel

  7. Novartis Pharma AG, Basel, Switzerland

    Paul Burgess

  8. Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA

    Stacey Kalambakas & Yasser Mostafa Kamel

  9. Center Hospital of the Ardenne, Libramont, Belgium

    Frederic Forget

Authors
  1. Eric S. Winer
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  2. Howard Safran
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  3. Boguslawa Karaszewska
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  4. Sebastian Bauer
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  5. Dilawar Khan
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  6. Steffen Doerfel
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  7. Paul Burgess
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  8. Stacey Kalambakas
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  9. Yasser Mostafa Kamel
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  10. Frederic Forget
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Corresponding author

Correspondence to Eric S. Winer.

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Conflict of interest

EW, HS, BK, and SD have nothing to disclose. SB has provided consultancy for Blueprint Medicine, Novartis, and Pfizer. DK received honoraria from and provided consultancy for Incyte, Pfizer, and Pharmacyclics. PB held stock in and was an employee of GSK during the time of the study conduct and is now an employee of Novartis Pharma AG. SK was an employee of Novartis Pharmaceuticals Corporation and holds stock in Novartis. YMK was an employee of GlaxoSmithKline (GSK) during the time of study conduct and Novartis Pharmaceuticals Corporation, held GSK stock, and received travel accommodations and expenses from GSK. FF has received research funding from GSK.

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Winer, E.S., Safran, H., Karaszewska, B. et al. Eltrombopag for thrombocytopenia in patients with advanced solid tumors receiving gemcitabine-based chemotherapy: a randomized, placebo-controlled phase 2 study. Int J Hematol 106, 765–776 (2017). https://doi.org/10.1007/s12185-017-2319-9

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  • DOI: https://doi.org/10.1007/s12185-017-2319-9

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