Continuous Monitoring and Timely Intervention to Improve Adherence to AHT

Among Breast Cancer Patients

Research Scientist II

Research & Evaluation

Southern California Permanente Medical Group

Kaiser Permanente Southern California

HMO Research Network April 30, 2012

Virginia P. Quinn, PhD

Co-Authors

Justin Strauss, MA

Joanne Schottinger, MD

T.Craig Cheetham, PharmD

Acknowledgements

Chantal Avila, Joanie Chung, Alice Fisher, Reina Haque, Gerri Salazar, Jiaxiao Shi

Funding: Cancer Research Network & KPSC Community Benefit Program

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

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)

KPSC Service Area

Map of Kaiser Permanente

Southern California region

with hospitals (diamonds),

medical office buildings

(circles) and other facilities

(triangles)

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

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

(

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

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.

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

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.

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.

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

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

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

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

Medication Possession Ratio (MPR)

Percent of Patients with MPR <80%by Number of Treatment Years

27%

31%

33%

37%

42%

19%

20%

23%

29%

36%

20%

20%

20%

22%

22%

0%

20%

40%

60%

80%

100%

1 Year 2 Years 3 Years 4 Years 5 Years

Tam only AI only Tam to AI

Tam only (n=) 2,604 1,898 1,379 1,063 774AI only (n=) 2,713 1,848 1,156 567 237

Tam to AI (n=) 1,913 1,818 1,647 1,453 1,213

Discontinuation by Treatment Year

Cumulative Discontinuationby Number of Treatment Years

0%

5%

10%

15%

20%

25%

30%

Within 1Year

Within 2Years

Within 3Years

Within 4Years

Within 5Years

Tam Only AI Only Tam to AI

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

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)

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