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Patient-reported outcomes in the phase 3 BFORE trial of bosutinib versus imatinib for newly diagnosed chronic phase chronic myeloid leukemia

  • Jorge E. CortesEmail author
  • Carlo Gambacorti-Passerini
  • Michael W. Deininger
  • Michael J. Mauro
  • Charles Chuah
  • Dong-Wook Kim
  • Dragana Milojkovic
  • Philipp le Coutre
  • Valentin Garcia-Gutierrez
  • Rocco Crescenzo
  • Carla Mamolo
  • Arlene Reisman
  • Andreas Hochhaus
  • Tim H. Brümmendorf
  • the BFORE Study Investigators
Original Article – Clinical Oncology

Abstract

Background

In the phase 3 BFORE trial (NCT02130557), treatment with bosutinib resulted in a significantly higher major molecular response rate at 12 months versus imatinib in the modified intent-to-treat (mITT) population of patients with newly diagnosed chronic phase chronic myeloid leukemia (CP CML). Assessment of patient-reported outcomes (PROs) was an exploratory objective.

Methods

Patients with newly diagnosed CP CML were randomized 1:1 to receive once-daily bosutinib 400 mg or imatinib 400 mg as first-line therapy. Patients completed the Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu) and EuroQoL-5 Dimensions (EQ-5D) questionnaires at baseline, every 3 months for the first 24 months of treatment, every 6 months thereafter, and at treatment completion. We report PRO results at month 12 in the mITT population (bosutinib: n = 246; imatinib: n = 241).

Results

Mean FACT-Leu combined and subscale scores were similar at baseline in the bosutinib and imatinib arms; at month 12, all scores demonstrated improvement or maintenance of health-related quality of life (HRQoL) in both treatment arms. Repeated-measures mixed-effects models showed no significant difference between bosutinib and imatinib for any FACT-Leu score. Functional health status, as measured by EQ-5D, also demonstrated improvement or maintenance with bosutinib and imatinib at month 12.

Conclusions

Similar improvements in PROs compared with baseline were seen after 12 months of treatment with first-line bosutinib or imatinib in the BFORE trial. Newly diagnosed patients with CP CML receiving bosutinib or imatinib can preserve or improve HRQoL during treatment, although clinical efficacy was superior with bosutinib.

Keywords

Bosutinib Chronic myeloid leukemia Health-related quality of life Imatinib Patient-reported outcomes 

Notes

Acknowledgements

This study (ClinicalTrials.gov, NCT02130557) was sponsored by Avillion LLP under a collaborative development agreement with Pfizer Inc. Medical writing support was provided by Joanna Bloom, PhD, of Engage Scientific Solutions and was funded by Pfizer. The authors would like to thank Irina Dyagil for her contributions to collection, assembly, and analysis of data, and Laurence Reilly and Allison Jeynes-Ellis of Avillion LLP, London, UK, for their contributions to study design and data analysis.

Funding

This study was sponsored by Avillion LLP under a collaborative development agreement with Pfizer Inc.

Compliance with ethical standards

Conflict of interest

JEC: consultancy (ARIAD, Bristol-Myers Squibb, ImmunoGen, Novartis, Pfizer, Takeda) and research funding (ARIAD, Bristol-Myers Squibb, ImmunoGen, Novartis, Sun Pharma, Pfizer, Takeda, Teva). CG-P: consultancy (Bristol-Myers Squibb) and honoraria and research funding (Pfizer). MWD: advisory board (Blue Print, Pfizer, Ascentage Pharma, and Humana), consultancy (Blue Print, Pfizer, Ascentage Pharma, and TRM), research funding (Pfizer), and study management committee (Blue Print and Takeda). MJM: consultancy (Bristol-Myers Squibb). CC: honoraria (Bristol-Myers Squibb, Chiltern, Novartis, and Otsuka) and travel (Pfizer). D-WK: consultancy (Bristol-Myers Squibb, Il-Yang, Novartis), honoraria, and research funding (Bristol-Myers Squibb, Il-Yang, Novartis, Pfizer), membership on board of directors or advisory committees (Bristol-Myers Squibb), and speakers bureau (Bristol-Myers Squibb, Novartis, Pfizer). DM: consultancy and honoraria (ARIAD, Bristol-Myers Squibb, Novartis, Pfizer) and honoraria and speakers bureau (Incyte). PlC: honoraria (ARIAD, Bristol-Myers Squibb, Incyte, Novartis, Pfizer) and research funding (Novartis). VG-G: consultancy, honoraria, and research funding (Bristol-Myers Squibb, Incyte, Novartis, Pfizer). RC: equity ownership (Pfizer and GlaxoSmithKline). CM: employment and equity ownership (Pfizer). AR: employment (Pfizer). AH: research funding (Bristol-Myers Squibb, Incyte, Novartis, Pfizer). THB: consultancy (Novartis, Pfizer, Janssen, Merck, Takeda) and research funding (Novartis, Pfizer).

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

432_2019_2894_MOESM1_ESM.docx (523 kb)
Supplementary material 1 (DOCX 523 KB)

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Copyright information

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

Authors and Affiliations

  • Jorge E. Cortes
    • 1
    Email author
  • Carlo Gambacorti-Passerini
    • 2
  • Michael W. Deininger
    • 3
  • Michael J. Mauro
    • 4
  • Charles Chuah
    • 5
  • Dong-Wook Kim
    • 6
  • Dragana Milojkovic
    • 7
  • Philipp le Coutre
    • 8
  • Valentin Garcia-Gutierrez
    • 9
  • Rocco Crescenzo
    • 10
  • Carla Mamolo
    • 11
  • Arlene Reisman
    • 12
  • Andreas Hochhaus
    • 13
  • Tim H. Brümmendorf
    • 14
  • the BFORE Study Investigators
  1. 1.University of Texas MD Anderson Cancer CenterHoustonUSA
  2. 2.University of Milano-BicoccaMonzaItaly
  3. 3.University of UtahSalt Lake CityUSA
  4. 4.Memorial Sloan Kettering Cancer CenterNew YorkUSA
  5. 5.Singapore General HospitalDuke-NUS Graduate Medical SchoolSingaporeSingapore
  6. 6.Seoul St. Mary’s Hematology Hospital, Leukemia Research InstituteThe Catholic University of KoreaSeoulRepublic of Korea
  7. 7.Hammersmith HospitalImperial College LondonLondonUK
  8. 8.Charité-Universitätsmedizin BerlinBerlinGermany
  9. 9.Hospital Universitario Ramón y CajalIRYCISMadridSpain
  10. 10.Pfizer IncCollegevilleUSA
  11. 11.Pfizer IncGrotonUSA
  12. 12.Pfizer IncNew YorkUSA
  13. 13.Klinik für Innere Medizin IIUniversitätsklinikum JenaJenaGermany
  14. 14.Department of Hematology and OncologyUniversitätsklinikum RWTH AachenAachenGermany

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