Oral Oncolytics: Part 1—Financial, Adherence, and Management Challenges
Oral Oncolytics: Part 1—Financial, Adherence, and Management Challenges
The management of patients receiving treatment with oral oncolytics presents many challenges. Issues related to cost, adherence, monitoring of side effects and interactions, and safe handling create a vast web of complexity that makes the use of these agents far more challenging than the use of traditional intravenous oncolytics. Data are scarce on the management of oral chemotherapy patients, and the data that are available often only address a single issue related to the care of these patients. The fact is that each of the issues noted above creates a situation that is more complicated than has been depicted in most of the literature.
The Scope of the Problem
All of the above challenges are exacerbated—and made more urgent—by the changes that are occurring in anticancer drug development. If we look at the history of oral oncolytic drug approvals, we can see why the issues surrounding the use of oral anticancer agents are coming to the forefront of cancer care. After the first oral oncolytic was approved in 1953, the subsequent 50 years saw 27 oral agents approved for cancer treatment. This represents 1 new medication roughly every 2 years. Since 2004, 22 new oral agents have been approved in 9 years, indicating an approval rate of 1 new medication roughly every 5 months. If we look at just the last 5 years, there have been 15 new oral drugs approved, further increasing the average approval rate to 1 new drug every 4 months. New oral oncolytics are thus hitting the market 12 times faster than they were prior to 2003 (Figure). In addition, up to 35% of the agents in clinical trials are oral agents, making this an issue that will only grow in the future. Although some of these agents are for more atypical or rarer forms of cancer, such as vandetanib for medullary thyroid cancer or vismodegib for advanced basal cell carcinoma, some are for very common diseases, such as abiraterone or enzalutamide for castration-resistant prostate cancer. In some cases, the new oral agents represent drugs that formerly were available only in IV formulations (ie, methotrexate, fludarabine, and etoposide); others of the new oral agents are new multi-targeted kinases or hormonal antagonists.
This proliferation of oral agents has resulted in increased monitoring and care of patients on oral chemotherapy. At St. Luke’s Mountain States Tumor Institute, we showed that the addition of abiraterone to our institutional formulary increased our healthcare providers’ workload by approximately 15%. If new agents are being approved at a rate of 1 every 4 months, that could lead to nearly a doubling of workload in 2 years’ time. In order to keep up with workload requirements, institutions need to “work smarter”: they need to develop standard measures of care and monitoring that will enable them to optimize care of these patients.
It is our hope that this discussion of both the various challenges involved in managing patients receiving treatment with oral oncolytics, and possible solutions, will prove helpful. Next month, in a second article, we will discuss the ramifications of recent legislative activity both for patients receiving oral oncolytic therapy and for their physicians.
The Financial Challenge
Possibly the most significant day-to-day barrier to optimum management of oral oncolytics is the issue of cost. In 2009, oral oncology medication monthly out-of-pocket costs averaged $2,942, up 17% from 2008. An Avalere Health study found that almost 10% of patients choose not to fill their initial prescriptions for oral anticancer medications due to the high rates of cost-sharing. The literature reports primary nonadherence rates upwards of 20%, with the main reason given for nonadherence being cost.[5,6]
Most of the oral oncolytics currently available cost several thousand dollars per month (eg, lenalidomide, dasatinib, vemurafenib, to name a few), and the type or presence of insurance greatly influences the cost to patients and their likelihood of filling their prescription. Patients often fall into one of three financial categories: they are either uninsured or underinsured, they have private insurance, or they have government insurance (Medicare, Medicaid, Tricare, etc). Each of these groups presents unique obstacles to optimal fulfillment of oral oncolytic prescriptions. A working knowledge of the pathways associated with medication fulfillment can greatly reduce costs to the patients, the healthcare system, and the insurance companies. Patients who are uninsured can often get help directly from manufacturers, who can supply free medication for persons who qualify for medication assistance programs. Patients with private insurance often have high copays, but copay cards from manufacturers can often help reduce the cost to the patient. Lastly, patients on government insurance can have a wide range of prescription drug benefits. Some patients have supplemental insurance plans that help with the coverage gap, making their medications easy to manage. Other patients without prescription drug insurance or supplemental insurance may have copays up to 20% of the drug cost or more. Unfortunately, being on government insurance automatically precludes patients from utilizing manufacturer-based copay assistance programs. However, many nonprofit copay assistance programs exist that can help this group of patients (Chronic Disease Fund, Partnership for Prescription Assistance [PPARX], Care Care, etc). Collaborations with such programs can be arranged more easily on site, where interactions between pharmacists and financial advocates or social workers can happen quickly. This process of collaboration has been shown to reduce nonfulfillment rates while saving the patient money and reducing medication write-offs for unpaid pharmacy bills.
In a majority of cases, oral chemotherapy agents that are prescribed are issued by specialty pharmacies, and this may prevent patients from obtaining these medications at the time of diagnosis. In some cases, this problem can be overcome easily by having a discussion with the insurance company and getting on contract. However, some insurance companies only allow fills to go through a single mail-order pharmacy, in which case neither the patient nor the provider has any choice in how the patient obtains his or her medication. This is potentially problematic, since the direct lines of communication that exist between an internal pharmacy and the physician’s office do not exist with external pharmacies. In addition, if patients are required to use a mail-order pharmacy, they may never have the opportunity for direct interactions with the pharmacist, much less with a pharmacist who is a member of their healthcare team, and this may compromise optimal therapy.
In a majority of cases, physicians like to see their patients on the day of or a few days prior to the start of their next cycle of chemotherapy. Programs with on-site dispensing can prepare prescriptions for patients to pick up at their physician’s office after their visit to initiate their subsequent chemotherapy cycle. Mail-order pharmacies often have to send scripts via mail to arrive on or before a patient’s Day One cycle visit with his or her prescriber. This can be potentially wasteful, since any change in the prescription or discontinuation of the medication—which typically occurs on what would have been Day One of a cycle—can leave the patient with thousands of dollars of unused drug that cannot be returned for credit (once a medication is dispensed and leaves pharmacy control, legally it cannot be reused for another patient). A 6-month assessment of this issue was conducted at our site, based on utilization of an on-site pharmacy to fill all prescriptions. In that 6-month analysis, 37 patients discontinued medication on the start date of their next cycle after seeing their physician. This resulted in a total of $103,567.33 worth of medication (based on average wholesale price) that was able to be returned for credit, thereby saving the insurance companies money as well as saving patients $13,850 in copay costs, compared with the costs these parties would have incurred if a mail-order pharmacy had been used. Further analysis of this type of cost savings can show a significant overall reduction in healthcare costs associated with on-site dispensing.