Anthony Palmieri, PharmD, RPh, MBA

The use of specialty medications to treat an expanding number of conditions is growing at an impressive rate. As evidence of this, in 2010, only 3 specialty agents were in the list of top 10 drugs by revenue (representing 26%).

 By 2016, it is projected that 7 of the top 10 revenue drugs in the United States will be specialty agents (69% of revenue).

 This fact, along with the realization that hundreds of products are in the specialty pipeline awaiting approval, speaks to the need for more rigorous specialty management, especially for those drugs being utilized within the medical benefi t that are often unseen and unmanaged.1 Oral oncology is one example of a growing component of specialty that will shift drug use and fulfillment out of the medical benefit and place it into the pharmacy benefit. Insurers generally place oral oncology drugs under a patient’s pharmacy benefit; therefore, they are dispensed either within a retail setting or from a specialty pharmacy. It is to this end that these agents have become a focus of pharmacy benefit managers and pharmacy directors of various payers in the marketplace.

As we look back on 2011, we can see that the overall drug trend represented another year of slower gross trend. However, the specialty trend continued to have double digit increases, while nonspecialty had flat or negative movement due to the increase of generic utilization and minimal new molecular entities. Specialty pharmaceuticals continue to play a signifi cant role in drug spending growth. Factors promoting specialty growth include a wave of signifi cant launches and expansion of indications—both factors are increasing the impact to overall trend in drug spend. On a broad level, research and development efforts continue to focus on therapies to treat a wide range of cancers and will affect utilization trends. In addition, there is an increasing focus on oral cancer therapies to augment current injectable treatment options. This analysis will review the class cost, demographic profi le, and utilization trends of the oral antineoplastic enzyme tyrosine/multikinase inhibitor agents.

Cancer continues to be a major public health issue in the United States—1 in 4 deaths can be attributed to cancer.2,3 According to projections for 2012, it is estimated that there will be over 1.6 million new cancer cases and nearly 600,000 deaths from cancer (this figure does not include carcinoma in situ of any site except urinary bladder, nor does it include basal and squamous skin cancers).2 The most common cancers that cause death in men continue to be lung and bronchus, prostate, and colorectal; in women, the most common cancers that cause death are lung and bronchus, breast, and colorectal.

 Based on the experience of the general population, it is estimated that males (45%) have a greater lifetime probability of being diagnosed with an invasive cancer than females (38%).

Based on the most recent 5 years of mortality data (2004-2008), the overall cancer death rate decreased by 1.8% per year in males and 1.6% per year in females.

 Despite a decline in incidence for the major cancer sites, there are several cancers that are increasing—these include human papillomavirus (HPV)-related oropharyngeal cancer, esophageal adenocarcinoma, melanoma of the skin, and cancers of the pancreas, liver, and intrahepatic bile duct, thyroid, kidney, and renal pelvis.

The range of approved indications for currently marketed oral tyrosine/multikinase antineoplastic cancer drugs is shown in 

A retrospective claims analysis was conducted using CVS Caremark’s Book of Business (BOB) trend cohort for Employer and Health Plan clients using year to date (YTD) September 2011 versus YTD September 2010 claims data. The trend cohort clients represent CVS Caremark clients that have had a stable membership (variations not exceeding ± 20%) for at least 2 years. The Employer and Health Plan portion of the trend cohort represents 22 million lives. The cost per day and utilization trends were analyzed for selected oral antineoplastic enzyme inhibitor agents: imatinib (Gleevec, Novartis Pharmaceuticals Corporation, East Hanover, New Jersey), sorafenib (Nexavar, Bayer Health-Care Pharmaceuticals Inc, Wayne, New Jersey), dasatinib (Sprycel, Bristol-Myers Squibb Company, Princeton, New Jersey), sunitinib malate (Sutent, Pfizer Inc, New York, New York), erlotinib (Tarceva, OSI Pharmaceuticals, LLC, Farmingdale, New York), and nilotinib (Tasigna, Novartis Pharmaceuticals Corporation, East Hanover, New Jersey) (see Table 1 for a listing of selected US Food and Drug Administration—approved indications).

While many of the selected oral antineoplastic agents have seen a decrease in utilizers, dasatinib and nilotinib have seen a significant bump in utilizers when comparing YTD September 2010 with YTD September 2011 (

). All the oral antineoplastic tyrosine/multikinase inhibitors have seen an increase in the cost per claim during the same time period. 

 shows the demographic breakdown of utilizers for the selected agents.

While oral therapy oncology treatment adds convenience, it is not without serious concerns regarding patient monitoring and adherence. Although oral cancer drugs have been available in the marketplace for decades (eg, tamoxifen, methotrexate), there has been a rapid expansion in the last few years of new agents. This expansion raises serious concerns regarding adherence because their use shifts the site of drug administration from physician-monitored settings to the patient’s home. Due to the assumed perceived seriousness of a cancer diagnosis, some may believe that adherence would automatically be greater within this population and therefore not require intense monitoring, but that is not the case. In fact, adherence may even be lower than the 50% rate projected by the World Health Organization across all medication classes.

 One major reason for this is the reduced exposure to physicians and physician office staff oversight for patients administering oral drugs at home compared with patients taking their oncology medications intravenously. In general, there is a lack of infrastructure within physician offi ces to monitor proper administration of oral agents for patients at their home setting. This reduction in medical oversight involved in administration results in additional responsibility being placed on the patient to correctly adhere to and take his or her medication regimen. This problem was summed up well by Dr Ronald Walters of MD Anderson Cancer Center in Houston, Texas, when he stated that there is a “diffusion of responsibility that goes on in an oral chemotherapyprescription.”

Oral Oncology and Challenges to Adherence

According to a recent National Comprehensive Cancer Network task force report, one-fourth of all chemotherapeutic agents in development are expected to have an oral route of administration. Oral agents have transformed care for many patients, replacing long sessions in physicians’ offices for medication infusion services. Still, it is important that no distinction be set between oral and intravenous (IV) chemotherapy in terms of care, patient education, or monitoring.6 One important way to ensure this is to designate oral oncology drugs as specialty medications within the prescription benefit so that the same level of care coordination is provided to these agents as to their infused or injected counterparts. Oral oncology medications can be considered specialty because of several reasons, including the following: their use is associated with a chronic or complex disease state; they are generally high cost; they are part of a therapeutic class generally accepted as a specialty class; they carry the potential for highly prevalent and severe side effects; they often require advanced monitoring to avoid or identify serious adverse events; they require a considerable degree of administrative complexity for the patient; and regular dosing adjustments are possible in response to laboratory results, adverse events, and overall response to treatment.

While using oral oncology medications offers several advantages, not the least of which is convenience and the potential for less intense side effects compared with IV therapy, many issues can contribute to noncompliance within this population. Some important considerations when assessing a patient’s adherence to an oral oncology medication regimen include the patient’s education level regarding their regimen, diagnosis, and treatment; side effect management, especially now that the patient will have less exposure to healthcare professionals during the administration process; patient forgetfulness; challenges filling finding the medications (some pharmacies may not stock these agents due to their high acquisition costs); and patient out-of-pocket cost, especially for those patients who are subject to the Medicare Part D “donut hole” until catastrophic coverage is activated.

 In addition to these concerns, oral therapy comes with the complex issue of drug-food interactions and the possibility of drug-drug interactions that may differ from the drug’s IV counterpart or alternative.

The importance of even brief interactions with healthcare professionals while on oral oncology therapy can be significant. This is because a patient’s inability to adhere to his or her medication for cancer can negatively affect the treatment outcome. This can result in disease progression and even death. It has been shown that patients who use only 1 pharmacy for their prescription fulfi llment are 5 times less likely to fall off therapy,1 so a simple recommendation to patients would be to consolidate their pharmacy use for improved adherence.

From a class-specific perspective, there are many common and predictable side effects that can be expected with the use of tyrosine/multikinase inhibitors reviewed within this article. Simple recommendations such as avoiding sun exposure and using moisturizers can help manage the majority of patients who will experience some dermatological effect from these agents. Education about other potential side effects such as diarrhea can be appropriately managed with the use of OTC remedies. More serious monitoring for cardiac issues, which is seen with drugs such as sorafenib and sunitinib malate, can also be discussed with patients during prescription fulfi llment by pharmacists.

Another important benefit available to patients is the use of a specialty pharmacy. In general, specialty pharmacies can help facilitate the process of making the patient a more adherent consumer of oral oncology products. This can be accomplished in a number of important ways, such as providing expert consultation through the use of a case manager and clinical staff; delivering medication to the location of the patient’s choosing, often at no additional cost; improving access to medications by facilitating the use of patient assistance programs; creating a personalized care plan with actionable steps the patient can take to help understand the regimen and avoid unnecessary adverse events

; collecting and monitoring relevant laboratory data and therapeutic response parameters; and screening for common, often underreported comorbid events such as depression.

The development of and expanded use for oral oncology agents has given pharmacists and specialty pharmacies a unique opportunity to work with the patient during a critical time of treatment. The pharmacist-patient intervention can involve several facets of care, including the management of side effects, education of the patient on the importance of adherence, and guidance to ensure there is no interruption in treatment.

 It is essential to treat oral oncology no differently from IV therapy in regard to safety and monitoring—this will improve the likelihood of improved health and positive outcomes.

The cost of treatment with oral oncology therapies continues to increase. The oncology pipeline is robust, with a trend in oncology toward additional personalized medicines, as well as a continuation of the trend toward more oral therapies. As more oncology treatment options move from those that are administered in a doctor’s office or clinic to oral agents, we will continue to see the cost shift from the medical benefi t to the pharmacy benefit. Additionally, as more and more patients use oral therapies to treat their cancer, we need to recognize that adherence is an issue that will need to be addressed.

Articles

An overview of the utilization and cost for selected oral antineoplastic agents, with discussion regarding oncology in general, as well as the topic of adherence.