AcknowledgementsChantal Avila, Joanie Chung, Alice Fisher, Reina Haque, Gerri Salazar, Jiaxiao ShiFunding: 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 tamoxifenBurstein 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 doseHershman 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 mortalityHershman, Shao and Kushi et al. Breast Cancer Res Treat. 2011 Apr;126(2):529-37. Epub 2010 Aug 28.
Gaps are DangerousLarissa Nekhlyudov et al. found longer gaps in AHTtreatment were associated with lower likelihood ofresuming 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 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
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
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