The availability and popularity of orally administered anticancer therapy has drastically increased in recent years. Currently, there are more than 40 oral anticancer medications on the market in the U.S.; and about 40% of all newly FDA-approved anticancer agents in 2013 and 2014 have been oral agents. 1
The use of these agents is often driven by patients. In a review of 103 patients, an overwhelming 90% of patients who were to receive palliative chemotherapy chose oral chemotherapy over IV chemotherapy, assuming equivalent efficacy, toxicity, clinic visits, and blood work schedules. However, 70% of these patients were unwilling to sacrifice any efficacy between IV and oral chemotherapy. 2 Several other factors influenced the preference of oral chemotherapy for patients, including convenience, avoidance of central venous catheter placement or need for other IV access, control of the environment in which they receive chemotherapy, and travel considerations. 2 In addition to these practical benefits, patients reported a great sense of freedom with oral chemotherapy. 3
Although patients may prefer oral anticancer therapies, for providers, several issues exist surrounding the shift in delivery of anticancer therapies from IV to oral therapies. The most significant concern is patient adherence, defined as “the extent to which patients take medications as prescribed by their health care providers.” 4
Adherence rates in clinical trials are often excellent; however, real-life adherence rates tend to be less optimal. 5 In a study of women receiving 5 years of adjuvant tamoxifen for breast cancer, the researchers determined that patients filled their prescription 87% of the time the first year of treatment. This rate of adherence dramatically decreased to only 50% by year 4. 6
These results suggest that a longer duration of treatment can adversely affect adherence. Duration of treatment is of great concern for providers specifically when considering the need for indefinite duration of use of tyrosine kinase inhibitors for the treatment of chronic myeloid leukemia. In 2011, Ibrahim and colleagues showed that imatinib adherence rates of 85% have been directly correlated to the loss of complete cytogenetic response (26.8% vs 1.5%, P = .0002) and lower probability of continuing imatinib (64.5% vs 90.6%, P = .006). 7 Whereas several factors are known to influence adherence rates, Marin and colleagues identified the 2 main risk factors for poor adherence to imatinib: younger age and adverse effects (AEs). The median age for patients with adherence rates of 90% was 43.8 years compared with 53.8 years for patients with > 90% adherence rate. Imatinib AEs, such as asthenia, nausea, muscle cramps, and bone or joint pains, also significantly decreased imatinib adherence. 8
In addition to concerns for poor therapeutic outcomes and suboptimal toxicity management, lack of adherence to oral anticancer regimens can result in significant waste of medication and increased health care costs. In most situations, IV anticancer treatment cycles are repeated every 1 to 3 weeks and allow the patient more frequent face-to-face interaction with the oncology team. Oral chemotherapy, on the other hand, is traditionally dispensed as a 28- to 30-day supply. This practice often limits the patient’s access to the oncology team for full evaluation of adherence and toxicity, which can lead to oral anticancer therapy waste.
Khandelwal and colleagues investigated the utility of a split-fill to decrease health care costs. In the splitfill process, patients were dispensed only days 1 to 16 of their oral anticancer medication at the initial fill. If the medication was tolerated and the prescribing provider deemed no changes in treatment necessary, the remaining 12 to 14 days of the cycle were then dispensed. Unfortunately, all insurance companies did not authorize the split-fill plan, thus preventing some patients in the study to participate in this cost savings strategy. However, it was determined for the patients who discontinued therapy, about 34% could have reduced wastage had they been on the split-fill plan, resulting in an average direct savings of $934.20 per patient who discontinued use. 9
In 2011, the Hematology/Oncology and Pharmacy divisions at the VA Pittsburgh Healthcare System (VAPHS) examined the issues surrounding dispensing and monitoring of oral anticancer therapy. Higher utilization of oral anticancer therapy was identified and in parallel, increasing rates of patient nonadherence, toxicity, and wasted medication. Originally, most providers dispensed oral anticancer therapy as a 1-month supply. However, in efforts to increase adherence, limit toxicity, and avoid medication waste, some oncologists began only dispensing a 1- to 2-week supply of medication per visit. This shift in practice led to a pilot study evaluating the utility of limiting all oral chemotherapy to a 7- to 14-day supply during the first 3 months of treatment.