CLINICAL

CLINICAL

ORIGINAL RESEARCH

Patient Preferences and Treatment

Adherence Among Women Diagnosed
with Metastatic Breast Cancer
Marco daCosta DiBonaventura, PhD; Ronda Copher, PhD; Enrique Basurto, MSc; Claudio Faria,
PharmD, MPH; Rose Lorenzo, BA

Stakeholder Perspective,
page 396
Am Health Drug Benefits.
2014;7(7):386-396
www.AHDBonline.com
Received July 7, 2014
Accepted in final form September 16, 2014
Disclosures are at end of text
BACKGROUND: Given the various profiles (eg, oral vs intravenous administration, risk of hot flashes vs
fatigue) of treatment options (eg, endocrine therapy, chemotherapy) for metastatic breast cancer (mBC),
how patients value these attributes of their medications has implications on making treatment decisions
and on adherence.
OBJECTIVES: To understand how patients trade off medication side effects with improved effectiveness
and/or quality of life, to provide estimates of nonadherence among women with mBC, and to quantify the
association of medication nonadherence with health outcomes.
METHODS: The study was a cross-sectional, Internet-based survey of 181 women diagnosed with mBC
who were recruited from cancer-specific online panels (response rate, 7%). Treatment information, demo-
graphics, nonadherent behaviors, and quality of life assessed by the Functional Assessment of Cancer
Therapy-Breast (FACT-B) were collected in the survey, and each respondent completed a choice-based
conjoint exercise to assess patient preferences. The patients’ preferences were analyzed using hierarchi-
cal Bayesian logistic regression models, and the association between the number of nonadherent behav-
iors and the health outcomes was analyzed using general linear models.
RESULTS: The mean age of the patient sample was 52.2 years (standard deviation, ±9.1), with 93.9%
of participants being non-Hispanic white. Results from the conjoint model indicated that effectiveness
(overall survival) was of primary importance to patients, followed by side effects—notably alopecia, fatigue,
neutropenia, motor neuropathy, and nausea/vomiting—and finally, dosing regimen. In all, 34.8% of survey
respondents either discontinued their treatment or were nonadherent to their treatment regimen. Among
those who have ever used oral chemotherapy (N = 95; 52.5%) and those currently using oral chemother-
apy (N = 44; 24.3%), the number of nonadherent behaviors was significantly associated with a decrease
in functional well-being (b [unstandardized regression coefficient] = –2.01 for patients who had ever used
a targeted therapy and b = –3.14 for current users of a targeted therapy), FACT-General total score (b =
–4.30 and b = –7.37, respectively), FACT-B total score (b = –3.93 and b = –6.11, respectively), and FACT
trial outcome index (b = –5.22 and b = –8.63, respectively; all P <.05).
CONCLUSIONS: Patients were willing to accept substantial additional risks from side effects for gains in
overall survival. Approximately 33% of women with mBC reported engaging in nonadherent behaviors.
Because forgetfulness and adverse events were among the most frequent reasons for nonadherence,
these results suggest that less complex treatment regimens, as well as regimens with less toxic profiles,
may be associated with improvements in adherence and, subsequently, could correspond to perceptible
patient benefits.

B
reast cancer is the most common cancer diagnosed
among women in the United States, with an esti-
mated 232,000 new cases diagnosed annually.1 It is
Dr DiBonaventura is Vice President, Health Outcomes,
Health Outcomes Practice, Kantar Health, New York, NY;
Dr Copher is Associate Director, Health Economics and
Outcomes Research, Eisai Inc, Woodcliff Lake, NJ; Mr
Basurto is Senior Associate Methodologist, Kantar Health,
New York, NY; Dr Faria is Director, Health Economics and
Outcomes Research, Eisai Inc, Woodcliff Lake, NJ; and Ms
Lorenzo is Senior Director of Research, Kantar Health, New
York, NY.
also the second most deadly cancer, accounting for nearly
40,000 deaths annually.1 The 5-year survival rates for
early-stage breast cancer is between 84% for regional
disease (ie, contained within the breast and lymph nodes)
and 99% for localized disease (ie, contained within the
breast); the survival rate drops to 24% in more advanced
stages of the disease.2 Metastatic breast cancer (mBC) is
defined as breast cancer that has spread to other parts of
the body. Whereas less than 10% of women are initially
diagnosed with mBC, approximately 33% of women who
are treated for early-stage disease will progress to mBC.2,3
The majority of breast cancer metastases affect the lymph
nodes, followed by bone, liver, and lung.4,5

386 l American Health & Drug Benefits l www.AHDBonline.com October 2014 l Vol 7, No 7
 Patient Preferences in Metastatic Breast Cancer
At present, mBC is incurable, and treatment is fo-
cused on arresting the disease and extending patient
survival, as well as promoting quality of life (QOL) and
ensuring adequate symptom management.3,4 Treatment
strategies may include endocrine therapy (eg, exemes-
tane); targeted therapies, such as anti-HER2 agents (eg,
trastuzumab); and chemotherapy (eg, capecitabine).6 As
a result of the currently incurable nature of mBC and the
side-effect profile associated with various forms of thera-
py, investigators have explored the potential role of pa-
tient preferences in decision-making regarding their
treatment goals and desired outcomes.7-11 For example,
aggressive treatment may maximize the duration of sur-
vival but may also be associated with significant and
burdensome side effects that impair QOL.3,4
Using the responses of 102 patients with breast can-
cer, Beusterien and colleagues recently revealed distinct
preferences across side-effect profiles and a willingness to
undergo more difficult treatment regimens to reduce the
risk of more severe symptoms.7 Moreover, another study
of 121 patients with breast cancer demonstrated the im-
portance of a relatively minor survival benefit (as little as
3 months) for the perceived value of chemotherapy
among patients with breast cancer, despite an increased
risk for treatment toxicities.8 Further studies have shown
a willingness of patients to trade a minor increase in
disease recurrence risk for more convenient treatment
regimens,9 as well as examining patient preferences for
follow-up care10 and the ability for preferences to predict
the eventual use of chemotherapy.11
To our knowledge, no study to date has examined
patient preferences using a conjoint method in women
with mBC. In part, this may be because it is difficult to
recruit this patient population for research survey pur-
poses. Several studies have been conducted that have
focused on patients diagnosed with early-stage breast
cancer.12,13 McQuellon and colleagues surveyed women
diagnosed with early-stage disease to assess their prefer-
ences for the hypothetical treatment of mBC.14 Al-
though there was a wide range of preference profiles
among the women who were surveyed, they were once
again consistently willing to trade the risk of major side
effects and toxicities for a modest survival benefit.14
However, because that study was initiated nearly 20
years ago, treatment advances since the time of that
study were not included in that analysis.
The primary objective of the current study is to pro-
vide an examination of contemporary treatments and to
provide data on the treatment preferences of women
with mBC to understand how these patients trade off
side effects with increases in effectiveness and/or QOL.
Patient preferences may have implications not only
for treatment decision-making but also potentially for
Vol 7, No 7 l October 2014 www.AHDBonline.com
KEY POINTS
➤ Metastatic breast cancer (mBC) involves various
drug regimens with different efficacy and side-effect
profiles that may affect medication adherence.
➤ This is the first study to examine patient
preferences in women with mBC.
➤ Of the 181 women with mBC surveyed,
approximately 33% were nonadherent to their
treatment regimen.
➤ Patients receiving hormone therapy reported
the greatest nonadherence, followed by patients
receiving an oral chemotherapeutic agent.
➤ Across all treatment modalities, forgetfulness
(41.3%) and intolerance of side effects (36.5%)
were the most common reasons for nonadherence.
➤ Although it is more convenient, women receiving
oral chemotherapy were more likely to have
significant declines in their health status.
➤ Patients are willing to trade substantial side-effect
risks for gains in overall survival.
➤ The most important attributes of treatments were
effectiveness and side effects; cost-related concerns
were listed as the least important.
➤ The survey suggests that less complex and less toxic
regimens may improve medication adherence and,
ultimately, health outcomes.
treatment adherence and follow-up care.15 If patient
preferences and prescribed treatment regimens are mis-
aligned, women diagnosed with breast cancer may be-
come nonadherent, which could have implications for
symptom management and for survival.15 To date, much
of the research in this domain has focused on adherence
to adjuvant therapy in patients with early-stage dis-
ease.16-18 A secondary objective of this study is to provide
real-world evidence of nonadherence among women
with mBC and to quantify the association with nonad-
herent behavior and health outcomes. We focused on
adherence among patients receiving oral chemotherapy,
because these agents are increasing in availability, and
they represent a frequently self-administered treatment
(as opposed to intravenous treatment, which is often not
self-administered), and are thus more susceptible to non-
adherent behaviors.
Methods
Patient Sample and Procedures
Qualitative interviews. An initial qualitative study
was conducted to inform the participants of the survey.
A total of 10 telephone interviews were conducted using
a structured discussion guide with women who were di-
l American Health & Drug Benefits l 387
 CLINICAL

Table 1 Abbreviated Example of the Choice Task screening questions to determine eligibility; 28 respon-
dents were ineligible: 21 because they had never received
Q: Which treatment are you most likely to choose to treat a taxane and 7 because of unknown reasons or for having
your metastatic breast cancer?
Medicaid insurance coverage.
Measurement Treatment A Treatment B All participants who completed the survey were com-
Regimen 21-day cycle; 2- to 28-day cycle; 6- to pensated with a $100 donation made in their name to a
5-minute infusion 10-minute infusion nonprofit charitable organization of their choice. For
on days 1 and 8 on days 1, 8, and 15 both the qualitative interview and the participant sur-
Alopecia 48% chance of losing 94% chance of losing vey, all respondents provided informed consent and had
most or all of your most or all of your their responses kept confidential. The protocol was ap-
hair, thinning of hair, thinning of proved by an Institutional Review Board (Essex IRB;
eyebrows/eyelashes; eyebrows/eyelashes;
starts to grow back starts to grow back Lebanon, NJ).
within 2-3 months within 2-3 months
after receiving after receiving Survey Measures
chemotherapy chemotherapy Demographics and health characteristics. All partic-
Effectiveness Has shown an Has shown an ipants provided information about their age, race/ethnici-
additional survival additional survival ty, marital status, college education, annual household
benefit of 1 month benefit of 3 months income, employment, insurance type, and out-of-pocket
Quality of life Difficulty performing Difficulty performing (OOP) costs. Health-related information was also provid-
work or other activi- work or other activi- ed, such as height and weight, which was then converted
ties none of the time ties all of the time to a body mass index category of underweight (<18.5 kg/
m2), normal weight (18.5 to <25 kg/m2), overweight (25
agnosed with mBC. Patients were invited to participate to <30 kg/m2), obese (≥30 kg/m2), or missing (for those
through cancer-specific online panels (eg, the Find A participants who chose not to provide their weight). A
Cure Panel), which recruit members from cancer-orient- family history of breast cancer, years diagnosed, specialty
ed nonprofit Internet communities for the purpose of of diagnosing physician, stage at diagnosis, and months in
participating in research projects. metastatic stage were also reported.
To be eligible to participate in the study, women had Treatment history and adherence. The participants’
to report that they met the criteria, including being diag- treatment modality experience was defined by surgery,
nosed with mBC, aged ≥18 years, and be proficient in the intravenous chemotherapy, oral chemotherapy, radia-
English language. Patients who never received treatment tion therapy, hormone therapy, clinical trial medication,
with a taxane (eg, paclitaxel, docetaxel) or who did not and palliative care. The participants reported their expe-
have health insurance, were covered by Medicaid, or rience in terms of previous treatment and current treat-
who did not know their form of health insurance were ment. All women were asked whether they had been
excluded. These latter criteria were included to ensure nonadherent to or had discontinued any of their previ-
sufficient treatment experience to put our hypothetical ous treatments. For the participants who responded
treatments into context. For research questions that were affirmatively for nonadherence, specific reasons for non-
unrelated to the current study, the study focused on pa- adherence or discontinuation were provided, and re-
tients with private insurance types. Interviews lasted spondents were asked to indicate whether they engaged
approximately 30 minutes and focused on the patient’s in the behavior.
experience with previous treatments, as well as the fre- Quality of life. The Functional Assessment of Cancer
quency, severity, and tolerability of side effects. Therapy-Breast (FACT-B) was also included as a
Participant survey. The present study was a cross- health-related QOL (HR-QOL) measurement instru-
sectional, Internet-based survey of 181 women who were ment.19 The FACT-B includes the 7 subscales from the
diagnosed with mBC. The inclusion and exclusion crite- Functional Assessment of Cancer Therapy-General
ria of the women surveyed were identical to the qualita- (FACT-G)—physical well-being, social well-being,
tive participants. Potential participants were also invited family well-being, relationship with doctor, emotional
from cancer-specific online panels, the same source used well-being, functional well-being, trial outcome index—
in the qualitative research. A total of 2500 panelists were and the total score for the FACT-G. The FACT-B also
e-mailed invitations to participate in the current study includes a separate breast cancer subscale and a total
(response rate, 7%); those who clicked the invitation score (FACT-B total score) that combines all of the
link were directed to the statement of informed consent, subscales. For all of the subscales and total scores, higher
and, if consent was given, they were then directed to values reflect better HR-QOL.

388 l American Health & Drug Benefits l www.AHDBonline.com October 2014 l Vol 7, No 7
 Patient Preferences in Metastatic Breast Cancer

Stated preferences and choice task. Participants

Table 2 Patient Demographics
rated the importance of various attributes (from 1, indi-
cating “extremely important,” to 5, indicating “not at all Patient sample
(N = 181)
important”) and completed a choice-based conjoint task
consisting of 7 choice scenarios, each containing 2 pro- Age, mean, yrs (± SD) 52.2 (± 9.1)
files of hypothetical treatments. Participants then select- Non-Hispanic white, N (%) 170 (93.9)
ed the treatment they preferred from the 2 choices based
Married, N (%) 136 (75.1)
on the information in the profile; participants were told
to assume that all other attributes of the medications College graduate, N (%) 130 (71.8)
that were not explicitly mentioned in the profiles were Annual household income
identical (Table 1).
<$25,000, N (%) 11 (6.1)
For each profile of a hypothetical treatment in the
choice scenarios, 11 different attributes were comprised $25,000 to <$50,000, N (%) 31 (17.1)
of 8 safety attributes—including alopecia, motor neurop- $50,000 to <$75,000, N (%) 28 (15.5)
athy, myalgia/arthralgia, nausea/vomiting, fatigue, neu- ≥$75,000, N (%) 86 (47.5)
tropenia, mucositis/stomatitis, and diarrhea—1 effec-
tiveness attribute, 1 dosing regimen attribute, and 1 Decline to answer, N (%) 25 (13.8)
QOL attribute. The actual levels of each attribute varied Employment status
with every hypothetical profile and across all choice sce- Currently employed, N (%) 78 (43.1)
narios. These attributes were identified from the prelim-
inary qualitative research described earlier as well as an On leave from work, N (%) 15 (8.3)
examination of past literature. Retired, N (%) 31 (17.1)
Given the number of unique attribute-level combi- Other, N (%)
a 57 (31.5)
nations (ie, profiles), a fractional factorial balanced
incomplete block design was used. Kuhfeld’s SAS Health insurance
macros (SAS Institute; Cary, NC)20 were used to de- Private insurance, N (%) 162 (89.5)
rive a set of orthogonal arrays that were 99.9% D-effi- Medicare, N (%) 14 (7.7)
cient with respect to parameter variance. The result-
ing instruments had orthogonal profiles and balanced TRICARE, N (%) 5 (2.8)

attribute levels. Insurance coverage of breast cancer treatments

Covers all of my breast cancer 139 (76.8)
Statistical Analysis treatments, N (%)
The choice tasks were analyzed using hierarchical Covers some of my breast cancer
Bayesian logistic regression models, whereas the regres- 40 (22.1)
treatments, N (%)
sion models were parameterized using effects coding.
Does not cover any of my breast
The resulting model coefficients are viewed as part- cancer treatments, N (%)
1 (0.6)
worth utilities that also served as inputs to the relative
importance analysis. To understand the relative impor- Don’t know/not sure, N (%) 1 (0.6)

tance of the attributes, deviations of the part-worth Body mass index

utilities from the overall expected value were calculat- Underweight, N (%) 5 (2.8)
ed to create sums of squares for each individual attri-
bute; for each attribute, the regression coefficients for Normal weight, N (%) 67 (37)

each level of that attribute were squared and were Overweight, N (%) 61 (33.7)
summed together. The resulting sums of squares were Obese, N (%) 42 (23.2)
divided by the attribute-specific degrees of freedom to
Decline to provide weight, N (%) 6 (3.3)
generate a mean sum of squares (MSS) for each attri-
bute. The relative importance of each attribute was Information not available.
a

calculated by dividing the MSS for that attribute by the
sum of all MSS values for all attributes. The attributes
with higher relative importance have a disproportion-
ately larger MSS than other attributes, which is a result
of large coefficients of the individual levels. The indi-
vidual-level hierarchical Bayesian modeling was con-
SD indicates standard deviation.
ducted using Sawtooth’s CBC/HB v4.6.4 (Sawtooth
Software; Orem, UT).
Because they were significantly related to adher-
ence and associated with QOL, general linear models

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 CLINICAL

Table 3 Mean Out-of-Pocket Costs by Sociodemographic Categories

OOP breast OOP non– OOP non–
OOP breast cancer breast cancer breast cancer
cancer treat- physician treatment physician visit
Sociodemographic Patients, ment cost, $ visit cost, $ cost, $ costs, $
category N (%) mean (± SD) mean (± SD) mean (± SD) mean (± SD)
Total 181 (100) 302.94 (± 784.68) 107.43 (± 200.23) 27.06 (± 50.9) 11.94 (± 27.23)

Race
White 170 (93.92) 309.57 (± 806.86) 96.53 (± 145.67) 26.90 (± 52.08) 11.55 (± 27.53)

Non-Hispanic white 11 (6.08) 200.45 (± 261.55) 275.91 (± 574.32) 29.55 (± 27.88) 17.91 (± 22.34)

Education
College graduate 130 (71.82) 322.12 (± 842.74) 103.77 (± 210.08) 26.22 (± 50.8) 14.55 (± 31.09)

Less than college graduate 51 (28.18) 254.04 (± 617.15) 116.76 (± 174.2) 29.22 (± 51.58) 5.27 (± 10.59)

Salary
<$25,000 11 (6.08) 120 (± 241.59) 144.09 (± 229.41) 20.18 (± 59.77) 0 (± 0)

$25,000 to <$50,000 31 (17.13) 172.52 (± 255.24) 122.58 (± 187.31) 28.55 (± 39.82) 9.03 (± 17.48)

$50,000 to <$75,000 28 (15.47) 385.96 (± 977.93) 110 (± 154.87) 23 (± 49.39) 9.29 (± 21.33)

≥$75,000 86 (47.51) 389.01 (± 963.77) 100.35 (± 231.35) 29.67 (± 56.51) 16.41 (± 33.78)

Decline to answer 25 (13.81) 156.08 (± 228.67) 94 (± 130.69) 23.8 (± 42.73) 8.40 (± 21.4)

Enrolled in an assistance program

No 159 (87.85) 307.43 (± 826.02) 90.22 (± 136.58) 27.24 (± 51.8) 12.76 (± 28.49)

Yes 22 (12.15) 270.45 (± 377.87) 231.82 (± 429.95) 25.77 (± 44.9) 6 (± 14.4)

Region of United States

Midwest 51 (28.18) 586.96 (± 1355.39) 142.45 (± 203.63) 19.98 (± 43.97) 6.47 (± 18.09)

Northeast 37 (20.44) 198.27 (± 309.54) 83.11 (± 114.98) 43.51 (± 76.27) 15.41 (± 43.67)

South 48 (26.52) 189.96 (± 361.34) 116.77 (± 298.61) 19.94 (± 39.64) 12.54 (± 18.91)

West 44 (24.31) 190.98 (± 290.85) 77.27 (± 89.94) 29.82 (± 40.43) 14.41 (± 26.06)

Type of chemotherapy received at the time of the survey

Oral 44 (24.31) 313.45 (± 708.69) 107.05 (± 146.02) 26.86 (± 40.52) 8.8 (± 13.09)

Intravenous 76 (41.99) 501.8 (± 1099.4) 108.16 (± 156.14) 27.16 (± 53.41) 12.75 (± 30.23)

NOTE: All costs are independent of one another (eg, costs of breast cancer and costs not related to breast cancer do not
overlap).
OOP indicates out-of-pocket; SD, standard deviation.

controlling for age, race/ethnicity, education, and Results

body mass index were used to estimate the relation-
ship between the number of nonadherent behaviors
and QOL measured with the FACT-B (unstandard-
ized regression coefficients [ie, b] are provided, indi-
cating the effect on the dependent variable [ie, QOL]
with a 1-unit increase in the independent variable [ie,
nonadherent behaviors]). The effect of adherence was
examined separately among patients who had ever
received an oral chemotherapy agent (N = 95) and
those who were currently receiving an oral chemo-
therapy agent (N = 44).
Demographics and Health History
The mean age of the patient sample was 52.2 years
(standard deviation [SD], 9.1) with 93.9% of partici-
pants reporting being non-Hispanic white. The patients
were generally of high socioeconomic status, with 71.8%
of participants reporting having a college degree, 47.5%
reporting an annual household income of ≥$75,000, and
76.8% reporting that their insurance covers all of their
treatments for breast cancer (Table 2).
The total monthly OOP costs per patient were ap-
proximately $303 (SD, $785) for treatments related to

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 Patient Preferences in Metastatic Breast Cancer

breast cancer and approximately $107 (SD, $200) for Table 4 Stated Importance of Various Treatment Attributes
physician visits related to breast cancer (Table 3).
The OOP costs, particularly for the treatment of Importance for all
patients (N = 181),
breast cancer, were higher among patients who were Treatment attribute mean (± SD)
non-Hispanic white, were college educated, had a higher
household income, and were not enrolled in a patient How well the treatment helps in slowing 1.19 (± 0.44)
down the progression of the cancer
assistance program. Women in the Midwest United
States (28.18%) reported the highest cancer-related How these treatments can help in 1.22 (± 0.49)
extending my life
OOP costs (ie, $586.96).
The patients had extensive previous treatment expe- How effective the treatment is compared 1.41 (± 0.67)
rience across treatment modalities (100% intravenous with other treatments
chemotherapy, 82.3% surgery, 77.4% hormone therapy, The impact of the treatment on my 1.43 (± 0.59)
71.3% radiation therapy, and 52.5% oral chemothera- overall quality of life
py). The majority of participants (90.6%) were currently Appropriateness for the stage of my 1.51 (± 0.74)
receiving treatment, with the most common treatment breast cancer
modalities being hormone therapy (47.5%), intravenous The severity of the treatment side effects 1.57 (± 0.72)
chemotherapy (42%), and oral chemotherapy (24.3%).
The impact of the treatment on my ability 1.57 (± 0.68)
Patient Preferences to perform daily activities
When asked directly, the most important attributes of Ways to manage/cope with treatment 1.62 (± 0.70)
treatments for participants were related to effectiveness, side effects
followed by side effects. Cost-related attributes were the Potential side effects 1.79 (± 0.82)
least important (Table 4).
Potential safety risks 1.82 (± 0.80)
Results from the conjoint model reaffirmed the prima-
ry importance of effectiveness, as indicated by overall Long-term safety of the treatment 1.90 (± 0.91)
survival, followed by side effects (the most notable of
How the treatment actually works 1.95 (± 0.94)
which were alopecia, fatigue, neutropenia, motor neu-
ropathy, and nausea/vomiting), and, finally, dosing regi- The importance of following the 1.96 (± 1.05)
men (Table 5, Figure). For example, the logit column in prescribed dosing regimen
Table 5 represents the strength (and direction) of the The impact of the treatment on my 1.97 (± 0.87)
relationship between the presence of an attribute and mental health/emotional well-being
selecting that treatment. Survival of 3 months (5.24), How the treatment is administered/what 2.27 (± 1.07)
alopecia of 0% (1.70), and fatigue of 0% (1.19) had the the procedure involves
highest positive logits, suggesting the strongest relation- How long I would have to stay on the 2.27 (± 1.11)
ship with the probability of selection. treatment
Post-hoc analyses investigated whether these prefer-
Other patients’ experiences with the 2.51 (± 0.94)
ences would vary by treatment experience (ie, rounds of treatments
chemotherapy). Our findings suggest that patient prefer-
ence was remarkably consistent and did not vary by How long the treatment has been 2.78 (± 1.11)
available
treatment experience. In our analyses, all attributes were
rank ordered identically, and relative importance values Ways to help cover treatment 3.15 (± 1.37)
of any given subgroup were within 2% to 3% of any costs provided by the
pharmaceutical manufacturer
other subgroup. For example, the relative importance of
effectiveness attribute was highest for having received Cost of the treatment 3.24 (± 1.22)

more than 6 rounds of chemotherapy (34.51%) and low- Patient support programs provided by 3.42 (± 1.21)
est for having received less than 2 rounds of chemother- the manufacturer
apy (32.45%). Financial assistance for breast cancer 3.43 (± 1.31)
treatment from a charity or research
Adherence organization
A total of 63 (34.8%) survey participants either dis-
continued their treatment or were nonadherent to their NOTE: Rating scale was from 1 (extremely important) to 5 (not at
all important).
treatment regimen. Patients who had ever received hor- SD indicates standard deviation.
mone therapy (37.9%) reported the greatest level of

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 CLINICAL

Table 5 Part-Worth Utilities from the Conjoint Task

Attribute Levels Logit SE P value
Alopecia 0% 1.70 0.07 <.001
48% –0.61 0.05 <.001
94% –1.09 0.05 <.001
Motor neuropathy 0% 0.80 0.04 <.001
4% –0.24 0.02 <.001
10% –0.56 0.02 <.001
Myalgia/arthralgia 0% 0.22 0.02 <.001
4% –0.07 0.01 <.001
15% –0.16 0.01 <.001
Nausea/vomiting 0% 0.80 0.04 <.001
4% 0.04 0.01 .004
15% –0.84 0.04 <.001
Fatigue 0% 1.19 0.05 <.001
8% –0.16 0.02 <.001
24% –1.03 0.04 <.001
Neutropenia 0% 1.05 0.05 <.001
9% –0.26 0.03 <.001
23% –0.79 0.05 <.001
Mucositis/stomatitis 0% 0.21 0.01 <.001
5% –0.08 0.00 <.001
10% –0.13 0.01 <.001
Diarrhea 0% 0.31 0.02 <.001
5% 0 0.01 .699
15% –0.31 0.02 <.001
Effectiveness No survival benefit –4.98 0.19 <.001

Additional 1 month –0.26 0.05 <.001

Additional 3 months 5.24 0.18 <.001

Regimen 21-day cycle; oral tablets taken twice daily 0.30 0.01 <.001
for first 2 weeks
21-day cycle; 2- to 5-minute infusion 0.16 0.01 <.001
on days 1 and 8
21-day cycle; 3-hour infusion on day 1 0.05 0.01 <.001

28-day cycle; 6- to 10-minute infusion –0.02 0.01 .011

on days 1, 8, and 15
21-day cycle; 30-minute infusion –0.16 0.01 <.001
on days 1, 8, and 15
21-day cycle; 3-hour infusion –0.33 0.02 <.001
on days 1, 8, and 15
Quality of life Difficulty performing work or other 0.99 0.04 <.001
activities none of the time
Difficulty performing work or other 0.39 0.02 <.001
activities some of the time
Difficulty performing work or other –1.38 0.05 <.001
activities all of the time
SE indicates standard error.

392 l American Health & Drug Benefits l www.AHDBonline.com October 2014 l Vol 7, No 7
 Patient Preferences in Metastatic Breast Cancer

nonadherence, followed by patients who had ever re- Figure Relative Importance of Each Attribute
ceived an oral chemotherapy agent (36.8%). Across all
treatment modalities, forgetfulness (41.3%) and intoler-
Effectiveness 33.49%
ance of side effects (36.5%) were the most common
reasons for nonadherence among patients who reported Alopecia 21.32%
their nonadherence or discontinuation (Table 6). Fatigue 12.46%
Among the patients who had ever received an oral Neutropenia 10.37%
chemotherapy agent (N = 95), the number of nonadher-
Quality of life 7.69%
ent behaviors (mean, 1.57) was used to predict HR-QOL
(Table 7). Analogous models were also conducted Motor neuropathy 6.36%
among patients who were currently receiving a chemo- Nausea/vomiting 6.18%
therapy agent (N = 44). The number of nonadherent Diarrhea 1.08%
behaviors was significantly associated with a decrease in Myalgia/arthralgia 0.48%
functional well-being (b = –2.01 for patients who had
ever used a targeted therapy and b = –3.14 for current Mucositis/stomatitis 0.43%
users of a targeted therapy), FACT-G total score (b = Dosing regimen 0.14%
–4.30 and b = –7.37, respectively), FACT-B total score 0% 5% 10% 15% 20% 25% 30% 35% 40%
(b = –3.93 and b = –6.11, respectively), and FACT trial
Relative importance
outcome index (b = –5.22 and b = –8.63, respectively; all
P <.05).
Table 6 Reasons for Patient Nonadherence
Discussion
Patients who
The primary objective of this study was to assess pa- discontinued/were
tient preferences for the treatment of mBC, because most nonadherent,
of the existing literature focused on preferences among Reason stated N (%)
women with early-stage breast cancer. Although our re- Forgot to take medicines and/or keep 26 (41.3)
sults were generally comparable with the results of pa- treatment appointments
tients with early-stage disease,7,8 we found that treatment
I could not tolerate the side effects 23 (36.5)
effectiveness was rated as the most important attribute
among women with mBC, nearly twice as much as alo- Other a 19 (30.2)
pecia, and more than 3 times more important than other Had family obligations/an event to attend 10 (15.9)
side effects. The rank order of important attributes for a Side effects impacted my ability to perform 8 (12.7)
treatment is similar to the findings by Beusterien and daily activities
colleagues8; however, the current study estimated a
I was unable to enjoy everyday experiences 5 (7.9)
greater preference for treatment effectiveness and the
avoidance of alopecia, and a lower preference for regi- I could no longer afford the treatment 4 (6.4)
men and diarrhea. These findings help clarify the patient Treatment schedule was difficult to follow 3 (4.8)
perspective of treatments for mBC, which, if aligned I did not trust the medicine as it was still in 1 (1.6)
with prescribing patterns, may maximize treatment satis- clinical trials
faction and adherence.
I had to travel too far to get the treatment 0 (0)
A secondary objective of this study was to assess the
level of nonadherence for women with mBC who are Lack of support from family members/friend 0 (0)
receiving an oral chemotherapy agent and to establish I did not have someone to drive me to my 0 (0)
the relationship between nonadherence and QOL. Ap- treatment
proximately 33% of women with mBC reported engag- a
Additional information not available.
ing in medication nonadherent behavior. This rate is
consistent with previous reviews of treatment adherence apy agent were associated with significant decrements in
in patients with breast cancer.21 However, given the health status.
fairly affluent and engaged patient population, it can be Forgetfulness and adverse events were among the
hypothesized that adherence levels in the overall popu- most common reasons for nonadherence, and these re-
lation with mBC are even lower. Of note, even after sults suggest that a less complex treatment regimen and
adjusting for established predictors of QOL, the nonad- regimens with less toxic profiles may be associated with
herent behaviors of women receiving an oral chemother- improvements in adherence, and subsequently could

Vol 7, No 7 l October 2014 www.AHDBonline.com l American Health & Drug Benefits l 393
 CLINICAL

Table 7 A
 ssociation between the Number of Nonadherent Behaviors and FACT-B Scores Among Patients Who Ever
Received or Currently Receive an Oral Chemotherapy Agent
Social/ Breast Trial
Physical family Emotional Functional FACT-G cancer FACT-B outcome
well-being well-being well-being well-being total score subscale total score index
b b b b b b b b
Ever received an oral chemotherapy agent (N = 95)
Number of –1.00 (95% –0.90 (95% –0.39 (95% –2.01a (95% –4.30a (95% –0.92 (95% –3.93a (95% –5.22a (95%
nonadherent CI, –2.39 CI, –2.05 CI, –1.56 CI, –3.27 CI, –8.12 CI, –2.16 CI, –7.12 CI, –9.86
behaviors to 0.4) to 0.25) to 0.79) to –0.75) to –0.48) to 0.32) to –0.73) to –0.57)

R2 0.12 0.13 0.03 0.16 0.12 0.14 0.14 0.13

Currently receiving an oral chemotherapy agent (N = 44)
Number of –1.7 (95% –1.56 (95% –0.96 (95% –3.14a (95% –7.37a (95% –1.27 (95% –6.11a (95% –8.63a (95%
nonadherent CI, –3.76 CI, –3.44 CI, –2.64 CI, –4.82 CI, –12.98 CI, –3.1 CI, –10.72 CI, –15.53
behaviors to 0.36) to 0.31) to 0.72) to –1.47) to –1.75) to 0.56) to –1.5) to –1.73)

R2 0.23 0.13 0.14 0.30 0.22 0.18 0.22 0.21

a
P <.05.
b indicates unstandardized regression coefficient; CI, confidence interval; FACT-B, Functional Assessment of Cancer
Therapy-Breast; FACT-G, Functional Assessment of Cancer Therapy-General.

correspond to perceptible patient benefits. Other poten-
tial interventions may include greater education about
potential side effects (which could mitigate the influence
of side effects on nonadherence) and memory aids (eg,
reminder systems). Further research is necessary to un-
derstand these potential interventions and their effec-
tiveness in this patient population.
Targeted therapies have become increasingly impor-
tant in the treatment of many cancers, including breast
cancer.21 Such therapeutic agents are often taken orally
and can often have less severe side effects than tradition-
al chemotherapy regimens, which can improve patient
outcomes.22 Although these advantages can increase
adherence—because patients prefer oral therapies to
those administered intravenously—medication adher-
ence is complex. The complexity of adherence can be
influenced by a multitude of patient- and care-based
factors, including the prohibitive costs of targeted treat-
ments for some patients.21
Research examining adherence to targeted oral medi-
cations in the context of breast cancer has shown that
approximately 20% of patients are nonadherent, de-
pending on the way in which adherence was mea-
sured.22-24 Furthermore, in a study of adherence to lapati-
nib, Kartashov and colleagues reported that nonadherence
is associated with increased provider visits and suggested
an increase in the cost of care.23
Further research is needed to enhance our understand-
ing of the factors influencing adherence rates in the treat-
ment of breast cancer, and to develop effective interven-
tions in line with advances in the pharmaceutical industry.
A literature search did not uncover any epidemiology
study that could be useful to compare the general US
population of patients receiving treatment for mBC
against the sample in this current study.
Limitations
The results of the current study should be examined
within the context of its limitations. All data, including
treatments and adherence information, were self-report-
ed and could have been subject to recall biases and other
self-presentation effects. The conjoint task is a simplify-
ing hypothetical exercise to estimate how patients value
certain attributes of treatments, and may differ with the
inclusion of other relevant attributes or levels. For exam-
ple, in actual decision-making, the true benefit or risks
that will be experienced (eg, there is a probability of
certain survival outcomes, but not a guaranteed 3-month
survival) cannot be known with certainty. In addition,
differences in analytical methods and attributes can also
make it difficult to directly compare preference results
from one study to another.
Of note, the relationship between nonadherence and
QOL was presented in a single direction as nonadher-
ence predicting QOL. It is possible that the relationship
could be bidirectional (eg, QOL influencing adherence)
or that there could be additional third variables that are
not included in the current study that could explain the
relationships observed here. In addition, detailed infor-
mation on disease progression, treatment chronology,
side effects experienced, and dosing adjustments was
unavailable, so the context for the results on adherence

394 l American Health & Drug Benefits l www.AHDBonline.com October 2014 l Vol 7, No 7
 Patient Preferences in Metastatic Breast Cancer
is incomplete. For example, it is not known what the
mechanism was for the relationship between nonadher-
ence and health outcomes (eg, nonadherence leading to
faster disease progression leading to poorer QOL).
Finally, the current study used a convenience sample
of women with mBC. These women were generally of
high socioeconomic status, and, because of their partici-
pation in online oncology panels, may be more engaged
and/or knowledgeable about their condition and treat-
ments, which may influence their preferences, adher-
ence, and health outcomes.
Conclusion
The current study suggests that the treatment prefer-
ences of women diagnosed with mBC, an understudied
group in this context, are similar to the preferences of
women diagnosed with early-stage disease. Among the
patient sample surveyed, treatment effectiveness was of
primary importance, an effect that did not appear influ-
enced by other study variables. Further analysis revealed
that approximately 33% of the women surveyed reported
some degree of treatment nonadherence, which, in turn,
was associated with impairment of QOL among patients
receiving an oral chemotherapy agent. These results
have important implications for treatment planning in
the context of mBC, as well as reinforce the need to
consider medication adherence in promoting QOL and
desired treatment outcomes. ■
Acknowledgments
The authors would like to thank Duncan Brown,
PhD, for his contribution to the survey design and re-
cruitment of respondents. Dr Brown was a full-time em-
ployee of Kantar Health at the time of the study. The
authors would also like to thank Errol Philip, PhD, for
his assistance with the literature review and editorial
comments on the manuscript. Dr Philip is a paid consul-
tant to Kantar Health.
Funding Source
This study was funded by Eisai Inc.
Author Disclosure Statement
Dr DiBonaventura’s institution received research support
from Eisai Inc; Dr Copher is an employee of Eisai Inc; Mr
Basurto is a consultant to and received research support from
Eisai; Dr Faria is an employee of Eisai; and Ms Lorenzo’s
institution received research support from Eisai Inc.
Vol 7, No 7 l October 2014 www.AHDBonline.com
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Stakeholder Perspective next page
l American Health & Drug Benefits l 395
 CLINICAL
STAKEHOLDER PERSPECTIVE
Predicting Behavior: It’s a Matter of Preference
By Albert Tzeel, MD, MHSA, FACPE
Regional Medical Director, Medicare Operations, North Florida, Humana, Jacksonville
In the well-known quip that has been attributed to
individuals as diverse as the quantum physicist Niels
Bohr and the extraordinary baseball manager Casey
Stengel, both men are purported to have said, “I never
make predictions, especially about the future.” Predic-
tions, especially when they come to the ability and/or
desire to adhere to a medical regimen of care, are highly
dependent on a number of factors.
And so it is in the article by DiBonaventura and col-
leagues in this issue of American Health and Drug Bene-
fits.1 Not long ago, the paternalistic aspect of medical
care consisted of the physician prescribing a course of
medical care that was incumbent on the patient to fol-
low. Societal norms stipulated such behavior as a func-
tion of the asymmetric knowledge relationship between
a physician and a patient. As patients became more
empowered, they demanded a greater role in determin-
ing their own care, and we saw the genesis of the era of
“shared decision-making.” As Mazur discusses in his
book on shared decision-making, clarifying the notion of
this type of decision-making includes, among other
things, taking into account the risk preferences of pa-
tients.2 It is relatively easy for physicians and patients to
believe that they can and will conform to certain thera-
pies when they expect a relatively easy trade-off of
side-effect tolerance versus gains in survival time. How-
ever, experience does not always mirror expectation.
One reason for this lack of congruence between plan
and result may lie in behavioral economics. In their semi-
nal article on prospect theory, Kahneman and Tversky
posited and demonstrated that people make decisions
based on the potential value of losses and gains rather than
on the final outcome.3 In the article by DiBonaventura
and colleagues, women with metastatic breast cancer were
willing to trade increases in side effects for increases in life
expectancy.1 Of course, one could also argue that prospect
theory notes how people underweight the likelihood of
396 l American Health & Drug Benefits l www.AHDBonline.com
high probability events (eg, side effects from medical treat-
ment) while overvaluing the likelihood of lower probabil-
ity events (eg, cure in overall survival). This may also ex-
plain some of the findings encountered in the current
study by DiBonaventura and colleagues.
PAYERS: Payers understand these findings all too
well. In addition to being a HEDIS (Healthcare Effec-
tiveness Data and Information Set) measure, medication
adherence is an area of great interest, because of its over-
all impact on cost and outcomes. It is well-documented
that nonadherence to treatment, whether pharmacolog-
ic or otherwise, results in increased costs and worsened
health. Many payers have thus developed specialty ana-
lytic units to study and address the conundrum why pa-
tients are nonadherent to therapy.
PATIENTS: People often make decisions without
fully understanding the subconscious reasons why they
have chosen to act as they do. If individual patients
perhaps had more time or more inclination to truly
share their real perspectives, it is very possible that
there would be more adherence to treatment, or that
more appropriate therapy decisions would be made in a
shared manner in the first place. Of course, the key to
this occurring is to study why it is not currently hap-
pening. As DiBonaventura and colleagues note, per-
haps a decrease in the complexity of therapy may help
in that endeavor.1
Although we can certainly all hope for more under-
standing of patients’ preferences and their role in success-
ful care outcomes, what we cannot do, however, is predict
that this will actually happen. ■
1. DiBonaventura MdC, Copher R, Basurto E, et al. Patient preferences and treat-
ment adherence among women diagnosed with metastatic breast cancer. Am Health
Drug Benefits. 2014;7:386-396.
2. Mazur DJ. Shared Decision Making in the Physician-Patient Relationship. Tampa, FL:
American College of Physician Executives; 2001:103.
3. Kahneman D, Tversky A. Prospect theory: an analysis of decision under risk.
Econometrica. 1979;47:263-291.
October 2014 l Vol 7, No 7