Kaiser Permanente Southern California studied adherence to adjuvant hormonal therapy (AHT) among 10,827 breast cancer patients between 2000-2007. They found only 49% of patients took AHT as prescribed, with discontinuation rates reaching 25% by the fifth year. Continuous monitoring of pharmacy records is needed to identify underutilization early and develop timely interventions like reminder letters or calls to improve AHT adherence and outcomes.

1. Continuous Monitoring and Timely
Intervention to Improve Adherence to
AHT Among Breast Cancer Patients

2. Virginia P. Quinn, PhD
Research Scientist II
Research & Evaluation
Southern California Permanente
Medical Group
Kaiser Permanente Southern
California
HMO Research Network April 30, 2012

3. Co-Authors
Justin Strauss, MA
Joanne Schottinger, MD
T.Craig Cheetham, PharmD

4. Acknowledgements
Chantal Avila, Joanie Chung,
Alice Fisher, Reina Haque, Gerri
Salazar, Jiaxiao Shi
Funding: Cancer Research
Network & KPSC Community
Benefit Program

5. Kaiser Permanente Southern CA (KPSC)
• Serves 3.6 million members
• Diverse membership is generally
representative of population of southern
California
• Most members enrolled through employers
• ~200,000 enrolled through Medi-Cal
• ~400,000 Medicare enrollees
• 90% of members have comprehensive
drug coverage

6. KPSC Medical Care Program
• Medical care delivered in 14 medical
centers and 198 medical offices
• 5,300 physician partners in the
Southern California Permanente
Medical Group
• 76 FT medical oncologists (not counting
radiation, surgical, pediatric or
gynecologic oncologists)

7. KPSC Service Area
Map of Kaiser Permanente
Southern California region
with hospitals (diamonds),
medical office buildings
(circles) and other facilities
(triangles)

8. Breast Cancer Incidence
• 226,870 women will be diagnosed with
breast cancer in the US in 2012
• Each year, approximately 3000 women are
diagnosed with breast cancer in KPSC
• Breast cancer survival has increased since
the mid-1970s due to both screening and
improved treatment including adjuvant
hormonal drug therapy

9. Adjuvant Hormonal Therapy (AHT)
• AHT given after primary BCa treatment
• Hormonal tx deprives BCa cells of estrogen which
many BCa tumors need to grow
• Tamoxifen used for >30 yrs to treat early-stage,
as well as metastatic BCa
• Among the 75-80% of patients with early BCa
who have ER+ disease, tamoxifen immediately
reduces local, contralateral, and distant
recurrence by 50% and reduces breast cancer
mortality by 31%
• Early Breast Cancer Trialist Cooperative Group, 2005, 1988

10. Aromatase Inhibitors (AIs)
• More recently, third-generation aromatase inhibitors
(anastrozole, exemestane, and letrozole) have been
approved and recommended as AHT for post-
menopausal women with hormone-sensitive BCa
• These medications block estrogen production by the
body
• AIs have a modest increase in recurrence reduction
(typically <5%), though overall survival is equivalent
with tamoxifen when they are used as either a
primary or extended treatment strategy

11. ASCO Clinical Practice Guideline Update
• Postmenopausal women with hormone
receptor-positive BCa should consider
taking an AI during the course of adjuvant
treatment either as primary therapy or
after 2-3 years of tamoxifen
• Women who are pre- or perimenopausal at
diagnosis should be treated with 5 years
of tamoxifen
Burstein et al. J Clin Oncol. 2010 Aug 10;28(23):3784-96. Epub 2010 Jul 12.

12. Utilization of AHT
• Despite the demonstrated efficacy of AHT,
under-utilization of AHT is common
• Multiple studies have found 40-60% of
women don’t complete their recommended
courses of AHT

13. AHT Utilization in KPNC
• A recent study conducted in KPNC found only
49% of women took AHT for the full duration at
the optimal dose
Hershman and Kushi et al. J Clin Oncol. 2010 Sep 20;28(27):4120-8. Epub 2010 Jun 28.
• Adjusting for clinical and demographic variables,
both early discontinuation (HR 1.26, 95% CI
1.09-1.46) and non-adherence (HR 1.49, 95% CI
1.23-1.81) among those who continued were
independent predictors of mortality
Hershman, Shao and Kushi et al. Breast Cancer Res Treat. 2011 Apr;126(2):529-37.
Epub 2010 Aug 28.

14. Gaps are Dangerous
Larissa Nekhlyudov et al. found longer gaps in AHT
treatment were associated with lower likelihood of
resuming therapy.
Breast Cancer Res Treat (2011) 130:681-689.

15. Sources of Under-Utilization of AHT
• Non-initiation
• Medication adherence
• The extent to which a patient conforms to the
prescribed dosage and treatment interval
instructions
• Medication persistence
• Refers to a patient’s act of continuing the
medication for the prescribed duration

16. Measuring AHT Utilization
• Medication Possession Ratio (MPR) is commonly
used to measure patient adherence and
persistence to prescribed medications
• This ratio is calculated as the number of days
supply of medication dispensed during a specified
follow-up period (e.g., 1 year) divided by the
number of days from the first dispensing to the end
of the follow-up period
• MPR of 80% or higher is considered to be an
indicator of good medication adherence and
persistence

17. AHT Utilization in KPSC
• 10,827 women eligible for AHT
• Diagnosed 2000-2007
• KPSC SEER-Affiliated Cancer Registry
• Stage 0-III, ER/PR+
• Had pharmacy benefits
• Enrolled for at least 1 year from dx
• Mean follow-up was 3.75 years from dx
• Automated pharmacy records were used
to examine uptake and utilization of AHT

18. Under-utilization of AHT in KPSC
• Approx. 1 in 7 eligible patients (14%) did
not initiate AHT
• Across all AHT treatments, over 30% of
initiators had a MPR <80%
• Discontinuance began in year 1 (7%)
• Approximately 5% of AHT initiators filled only a
single prescription
• By years 4 and 5, discontinuance reached
22% and 25%, respectively

19. Medication Possession Ratio (MPR)
Percent of Patients with MPR <80%
by Number of Treatment Years
Tam only AI only Tam to AI
100%
80%
60%
40%
42%
37%
36%
33%
31%
20%
29%
27%
23%
22%
22%
19%
20%
20%
20%
20%
0%
1 Year 2 Years 3 Years 4 Years 5 Years
Tam only (n=) 2,604 1,898 1,379 1,063 774
AI only (n=) 2,713 1,848 1,156 567 237
Tam to AI (n=) 1,913 1,818 1,647 1,453 1,213

20. Discontinuation by Treatment Year
Cumulative Discontinuation
by Number of Treatment Years
Tam Only AI Only Tam to AI
30%
25%
20%
15%
10%
5%
0%
Within 1 Within 2 Within 3 Within 4 Within 5
Year Years Years Years Years

21. What’s Needed for Interventions to
Promote AHT Adherence?
• Early case identification
• Electronic pharmacy system for monitoring
AHT utilization
• Ability to assess reasons for under-
utilization on a continuing basis
• Ability to link women with clinicians to
address side effects and change
medications
• Patient-centered care

22. What to Do?
• Address risk factors for under-utilization
• Socioeconomic influences
• Side-effects of AHT medications
• Co-morbidities (medical & psych)
• Monitor under-utilization
• Develop effective interventions with
“reach”
• KPNC notification letter
• KPSC automated voice reminders (AVR)

23. Conclusions
• There is growing recognition that
improving utilization of AHT may be a key
strategy in improving BCa prognosis
• Surveillance of AHT medication is needed
across the recommended 5 years of
therapy
• Innovative approaches are beginning to be
developed and tested in community
settings