Long-term patient-reported outcomes from an open-label safety and efficacy study of bosutinib in Philadelphia chromosome-positive chronic myeloid leukemia patients resistant or intolerant to prior therapy

Abstract

Background: Health-related quality of life (HRQOL) in patients with chronic-phase chronic myeloid leukemia (CML) is important because of the requirement for long-term treatment. This study assessed HRQOL in bosutinib-treated patients with Philadelphia chromosome-positive CML and resistance or intolerance to 1 (chronic-phase second-line [CP2L]) or more (chronic-phase third-line [CP3L]) tyrosine kinase inhibitors who had 264 weeks or more of follow-up (ClinicalTrials.gov identifier NCT00261846).

Methods: Patient-reported HRQOL was assessed with the EuroQol 5-Dimensions Questionnaire (EQ-5D) and the Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu).

Results: In total, 284 and 119 patients composed the CP2L and CP3L cohorts, respectively. At treatment completion, more than 50% of the patients in the CP2L and CP3L cohorts completed the EQ-5D and FACT-Leu assessments. The EQ-5D and EQ-5D visual analog scale scores were stable in both cohorts throughout treatment. The mean FACT-Leu scores were generally stable over time but were lower in magnitude in the CP3L cohort versus the CP2L cohort. The FACT-Leu scale scores of a subset of patients with chronic diarrhea (CP2L, n = 101; CP3L, n = 30) were similar to the scores of the larger cohorts. Minimally important differences (MIDs) from baseline for the FACT-Leu scale scores were observed for the following: emotional well-being (EWB), Functional Assessment of Cancer Therapy-General (FACT-G) Total, FACT-Leu Total, and Functional Assessment of Cancer Therapy Trial Outcome Index (FACT-TOI) in the CP2L cohort and FACT-Leu Total in the CP3L cohort. Among patients with chronic diarrhea, MIDs were observed for EWB, FACT-G Total, FACT-Leu Total, and FACT-TOI in the CP2L cohort and for EWB, FACT-G Total, and FACT-Leu Total in the CP3L cohort.

Conclusions: HRQOL was maintained with long-term bosutinib treatment for patients with CP2L and CP3L CML. Cancer 2018;124:587-95. © 2017 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Keywords: bosutinib; chronic myeloid leukemia; patient-reported outcomes; quality of life; tyrosine kinase inhibitors.

Figure 1

EQ‐5D score changes from baseline by visit according to chronic myeloid leukemia phase. *P ≤ .05 for a within‐group comparison between the specified time point and baseline using the paired t test. CI indicates confidence interval; CP2L, chronic‐phase second‐line; CP3L, chronic‐phase third‐line; EOT, end of treatment/treatment completion; EQ‐5D, EuroQol 5‐Dimensions Questionnaire.

Figure 2

EQ‐5D VAS score changes from baseline by visit according to chronic myeloid leukemia phase. *P ≤ .05 for a within‐group comparison between the specified time point and baseline using the paired t test. CI indicates confidence interval; CP2L, chronic‐phase second‐line; CP3L, chronic‐phase third‐line; EOT, end of treatment/treatment completion; EQ‐5D, EuroQol 5‐Dimensions Questionnaire; VAS, visual analog scale.

Figure 3

FACT‐Leu scale score changes from baseline by visit and at treatment completion. The ranges of assessments for the listed scale scores within the CP2L cohort (n = 284) were 135 to 138 for week 60, 108 to 112 for week 120, 100 to 103 for week 168, 94 to 95 for week 216, 78 to 80 for week 264, and 171 to 174 at EOT. The ranges of assessments for the listed scale scores within the CP3L cohort (n = 119) were 41 to 43 for week 60, 28 to 30 for week 120, 27 to 29 for week 168, 23 to 24 for week 216, 12 to 14 for week 264, and 74 to 75 at EOT. The baseline values for the CP2L cohort were 22.96 (PWB), 21.17 (SWB), 17.76 (EWB), 19.09 (FWB), 81.04 (FACT‐G Total), 133.22 (FACT‐Leu Total), 94.28 (FACT‐TOI), and 52.16 (additional concerns). The baseline values for the CP3L cohort were 22.61 (PWB), 21.09 (SWB), 17.96 (EWB), 19.31 (FWB), 80.81 (FACT‐G Total), 132.50 (FACT‐Leu Total), 93.75 (FACT‐TOI), and 51.83 (additional concerns). *P ≤ .05 for a within‐group comparison between the specified time point and baseline using the paired t test. †Minimally important differences. Positive values indicate an improvement in HRQOL, and negative scores indicate reduced HRQOL. CI indicates confidence interval; CP2L, chronic‐phase second‐line; CP3L, chronic‐phase third‐line; EOT, end of treatment/treatment completion; EWB, emotional well‐being; FACT‐G, Functional Assessment of Cancer Therapy–General; FACT‐Leu, Functional Assessment of Cancer Therapy–Leukemia; FACT‐TOI, Functional Assessment of Cancer Therapy Trial Outcome Index; FWB, functional well‐being; PWB, physical well‐being; SWB, social/family well‐being.