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

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.

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Research data policy/data availability

Upon request, and subject to certain criteria, conditions and exceptions (see https://www.pfizer.com/science/clinical-trials/trial-data-and-results for more information), Pfizer will provide access to individual de-identified participant data from Pfizer-sponsored global interventional clinical studies conducted for medicines, vaccines and medical devices (1) for indications that have been approved in the US and/or EU or (2) in programs that have been terminated (i.e., development for all indications has been discontinued). Pfizer will also consider requests for the protocol, data dictionary, and statistical analysis plan. Data may be requested from Pfizer trials 24 months after study completion. The de-identified participant data will be made available to researchers whose proposals meet the research criteria and other conditions, and for which an exception does not apply, via a secure portal. To gain access, data requestors must enter into a data access agreement with Pfizer.

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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.

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Correspondence to Jorge E. Cortes.

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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).

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Cortes, J.E., Gambacorti-Passerini, C., Deininger, M.W. et al. Patient-reported outcomes in the phase 3 BFORE trial of bosutinib versus imatinib for newly diagnosed chronic phase chronic myeloid leukemia. J Cancer Res Clin Oncol 145, 1589–1599 (2019). https://doi.org/10.1007/s00432-019-02894-3

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Keywords

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