The Introduction of Generic Aromatase Inhibitors and Treatment Adherence Among Medicare D Enrollees

There are over twenty oral antineoplastics currently approved in the United States and dozens more on the horizon (1). Adjuvant tamoxifen therapy for hormone receptor–positive breast cancer was one of the earliest developed long-term oncologic therapies. When taken for five to 10 years, it reduces long-term breast cancer mortality by one-third to one-half (2–4). The newer aromatase inhibitors anastrozole, letrozole, and exemestane reduce cancer recurrence by an additional 50% (5) but also need to be taken either alone or after tamoxifen for at least five total years of endocrine therapy (5). Unfortunately, many breast cancer patients prescribed long-term oral therapies have trouble adhering to them (6). One-third to one-half of patients prescribed adjuvant endocrine therapy (ET) outside of clinical trials either discontinue or adhere poorly to their medication within the first three years of therapy (7–15). Endocrine therapy nonadherence has clinically important effects. In one large breast cancer cohort, poor adherence to tamoxifen or aromatase inhibitors as measured by prescription fills was associated with a reduction in survival of 4% to 8% (16). There is increasing evidence that patient out-of-pocket costs play an important role in endocrine therapy nonadherence (17,18). The aromatase inhibitors (AIs) are substantially more costly than the generic tamoxifen, and many insurers are requiring that patients pay higher out-of-pocket costs for more expensive medications (17,18). In one recent study, 27% of patients in 2005 to 2008 with commercial insurance paid over $30 monthly out-of-pocket for their adjuvant aromatase inhibitor; adherence in this high-copay group was 18% to 28% lower than for patients paying $10 or less (17). In July 2010, an opportunity for reversal of these trends arose with the patent expiration of anastrozole. In contrast to some generic medications that face little competition when first released, thirteen generic manufacturers had generic anastrozole approved by the month after patent expiration, offering the potential for competition by cost. Shortly thereafter (April 2011), generic letrozole and exemestane were also released. Medicare D pharmaceutical program enrollees comprise an ideal national, population-based cohort in which to examine the adherence effects of this natural experiment. The Medicare D program required that all antineoplastic agents be on plan formularies. Furthermore, it provided a low-income subsidy (LIS) program to a substantial number of Medicare D enrollees, providing premium, deductible, and copayment support (including during the coverage gap or “donut hole” period) for enrollees with household incomes up to 150% of the federal poverty line. LIS recipients who experienced small or no effects upon out-of-pocket costs as generics became available thus could be compared with those without such supports, who experienced substantial changes in costs (18). The purpose of this study was to examine the effect of the introduction of generic versions of aromatase inhibitors on adherence to endocrine therapy among a nationally representative sample of elderly women with incident breast cancer using a quasi-experimental pre-post study design. We hypothesized that the well-documented rate of decline in adherence over time would be substantially attenuated after generic AIs became available. We further hypothesized that the effects would be larger for those not enrolled in the low-income subsidy program for pharmaceutical coverage.