Impact of Adverse Events on Health Utility and Health-Related Quality of Life in Patients Receiving First-Line Chemotherapy for Metastatic Breast Cancer: Results from the SELECT BC Study

PharmacoEconomics (2018) 36:215–223 https://doi.org/10.1007/s40273-017-0580-7 ORIGINAL RESEARCH ARTICLE Impact of Adverse Events on Health Utility and Health-Related Quality of Life in Patients Receiving First-Line Chemotherapy for Metastatic Breast Cancer: Results from the SELECT BC Study Yasuhiro Hagiwara1 • Takeru Shiroiwa2 • Kojiro Shimozuma3 • Takuya Kawahara4 Yukari Uemura4 • Takanori Watanabe5 • Naruto Taira6 • Takashi Fukuda2 • Yasuo Ohashi7 • Hirofumi Mukai8 • Published online: 17 October 2017 Ó The Author(s) 2017. This article is an open access publication Abstract Objective The aim of this study was to investigate the impact of adverse events (AEs) on health utility and healthrelated quality of life (HRQOL) in patients with metastatic breast cancer undergoing first-line chemotherapy. Methods We analyzed the data from the SELECT BC study, a multicenter, open-label, randomized, phase III study conducted in Japan, which compared first-line S-1 Electronic supplementary material The online version of this article (doi:10.1007/s40273-017-0580-7) contains supplementary material, which is available to authorized users. & Yasuhiro Hagiwara 1 Department of Biostatistics, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan 2 Department of Health and Welfare Services, National Institute of Public Health, Wako, Japan 3 Department of Biomedical Sciences, College of Life Sciences, Ritsumeikan University, Kusatsu, Japan 4 Biostatistics Division, Clinical Research Support Center, The University of Tokyo Hospital, Tokyo, Japan 5 Department of Breast Surgery, National Hospital Organization Sendai Medical Center, Sendai, Japan 6 Department of Breast and Endocrine Surgery, Okayama University Hospital, Okayama, Japan 7 Department of Integrated Science and Engineering for Sustainable Society, Faculty of Science and Engineering, Chuo University, Tokyo, Japan 8 Department of Breast and Medical Oncology, National Cancer Center Hospital East, Kashiwa, Japan with taxane therapies. Heath utility and HRQOL were assessed using the EQ-5D-3L and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) at baseline and 3, 6, and 12 months after treatment initiation. Health utility was calculated based on societal preferences, and AEs were reported at each cycle of the study treatment. Linear marginal mean models were used to quantify the impact of the last AEs (with 10 or more incidences) observed before HRQOL assessment on health utility and HRQOL. Results Analysis included 380 patients and 12 (of 15) AEs. Grade 1 nausea and oral mucositis, grade 1 and 2 edema, and grade 2 fatigue, motor and sensory neuropathy, and myalgia were significantly associated with disutility, measured using the EQ-5D-3L. Grade 1 oral mucositis, grade 1 and 2 fatigue, and grade 2 sensory neuropathy were significantly associated with impaired global health status in the EORTC QLQ-C30. AEs associated with decrements in the five functioning scales included fatigue, oral mucositis, nausea, edema, motor and sensory neuropathy, and myalgia. Conclusions We reported disutilities caused by AEs in patients with metastatic breast cancer under chemotherapy. These findings can be applied to future model-based costeffectiveness analyses. Trial Registration Number C000000416. 216 Key Points Analysis of EQ-5D and adverse event data in a randomized trial revealed that nausea, oral mucositis, edema, fatigue, motor and sensory neuropathy, and myalgia were significantly associated with disutility in patients receiving first-line chemotherapy for metastatic breast cancer. These disutilities directly measured from patients can be applied to future model-based costeffectiveness analyses for better decision making regarding medical resource allocation. 1 Introduction Breast cancer remains the most common malignancy in women, with an estimated 1.7 million diagnosed cases and 521,900 mortalities worldwide in 2012 [1]. For metastatic breast cancer, the goal of treatment is to prolong survival time and maintain a good quality of life. Although endocrine therapy is standard for certain breast cancer types, chemotherapy is recommended for others, or in endocrine therapy-resistant cases [2]. Chemotherapy effectively prolongs survival time [3, 4] but often induces a variety of adverse events (AEs). Effective medical resource allocation requires evaluation of not only clinical effectiveness but also cost effectiveness [5]. Model-based analysis plays an important role in assessing the cost effectiveness of chemotherapy drugs, when several sources of data should be combined [6, 7]. In model-based cost-effectiveness analysis, health utility values for each health state are required to calculate quality-adjusted life-years (QALYs) [8]. For example, the remaining life of a metastatic breast cancer patient can be divided into two health states: pre-progression and postprogression states. Health utility values of each state are used as quality weights for the time spent in each state, and disutility caused by AEs are accounted for by subtracting the impact of AEs from the health utility values of each state. Several researchers have reported the impact of chemotherapy-induced AEs on health utility in metastatic breast cancer patients [9–13]. However, few studies using vignette-based methods, such as the standard gamble and time trade-off methods, obtained health-related quality of life (HRQOL) directly from patients [9, 12]. Some guidelines recommend that HRQOL used in cost-effective analysis be measured directly from patients and then valued based on societal preferences [14–17]. Although one report on the impact of AEs on the EQ-5D-3L index, Y. Hagiwara et al. measured from metastatic breast cancer patients, is available, this study was conducted in a single institution with a small sample size, and the analysis pooled all grades to one category [18]. These limitations led to imprecise and inaccurate estimates. Additional studies for disutility caused by AEs using patient HRQOL data are required. The aim of this study was to investigate the impact of AEs on health utility, measured using the EQ-5D-3L, in metastatic breast cancer patients receiving first-line chemotherapy. We previously reported the long-term EQ5D-3L index results from the SELECT BC study, a Japanese multicenter, open-label, randomized, phase III study comparing the oral fluoropyrimidine derivative drug S-1 with taxane as first-line chemotherapy for metastatic breast cancer [19]. The results included health utility values before progression, after progression, and immediately before death. In this study, we used the same EQ-5D-3L data as from the SELECT BC study to estimate disutility caused by AEs. To support interpretation, we also reported the impact of AEs on HRQOL, measured by the European Organization for Research and Treatment of Cancer Quality of L (...truncated)