Antineoplastic Enzyme Inhibitor Drug Trend Utilization in the United States

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The American Journal of Pharmacy Benefits, June 2010, Volume 2, Issue 3

Increases in the number of cancer cases being diagnosed and treated likely will drive cost trends for antineoplastic enzyme inhibitors.

The number of new cases of cancer diagnosed annually in the United States increased from approximately 1.2 million in 2000 to 1.5 million in 2009.1,2 In 2009, approximately 562,000 people lost their lives due to some form of cancer.1,2 These fi gures, although tragic, represent a signifi cant improvement in cancer survivability, as the number of persons diagnosed increased 21.2%, but the increase in mortality was 1.8%. When adjusting for overall population increases, the mortality rate actually declined. Early diagnosis, treatment, and the availability of more antineoplastic drugs have contributed to the decrease in mortality rate.


Cancer cells reproduce at an abnormally faster rate than normal cells due to a disorder in the DNA of the cell that essentially tells it to divide in order to survive.3 Cancer types are determined by the point of origin because the replicating cancer cells resemble those in the original organ. For example, if a patient’s non—small cell lung cancer metastasizes to the liver, the patient has lung cancer, not liver cancer.

More than 100 drugs are used as monotherapy, concomitant, and/or adjuvant therapy to treat several forms of cancer, with the treatment protocol dependent on the nature of the organ involved. One of the latest oncologic drug classes is antineoplastic enzyme inhibitors, which are less invasive than several other forms of cancer treatment and are available as oral agents.

Antineoplastic enzyme inhibitors are used as targeted systemic therapeutic drugs that work to interfere with cell communication and growth.4 More specifi cally, these oral medications target and kill cells in the process of reproducing themselves by either (1) blocking cell receptors and/or (2) blocking blood/oxygen supplies to the cell, preventing angiogenesis. If successful, the treatment prevents the proliferation of abnormal cell growth that can lead to cancer. Unfortunately, the drugs also may affect other normal cells that commonly reproduce quickly, including hair follicles, ovaries and testes, and the blood-forming organs.

The majority of drugs in the class are tyrosine kinase inhibitors that focus on certain types of abnormal tyrosine kinase protein receptors (which types depend on the organ involved). To gain maximum effect, antineoplastic drugs are commonly used in combination with other forms of drug therapy or procedures (see

eAppendix A

for definition of cancer terms at Antineoplastic enzyme inhibitors are approved by the US Food and Drug Administration (FDA) for several indications, including adjunct therapy uses.

Table 1

provides a selected list of these indications.5


The analysis is a retrospective study of 23.2 million members who had more than 240 million prescription claims. CVS Caremark’s computerized, deidentified database was used to study the utilization of antineoplastic enzyme inhibitors from January 1, 2008, through December 31, 2009. The population identified for the study consisted of members across a variety of plan sponsors including Medicaid, national and local employers, health plans, managed care organizations, insurance companies, unions, and government agencies located throughout the United States.

The members had claims in 2008 and 2009, categorized by generation with the following dates of birth: 1900-1925 (GI Generation); 1926-1945 (Silent Generation); 1946-1964 (Baby Boomers); 1965-1978 (Generation X); 1979-1990 (Generation Y); and 1991 to the present (Generation Z).6 In addition to categorizing utilizers by age band, we also separated metrics by sex.

FINDINGSMarket Share

In 2009, Gleevec had 48.0% of all antineoplastic enzyme inhibitor days supply (market share), followed by Tarceva, which had 22.2%. Afinitor, recently approved and available in April 2009, acquired 1.2% market share. Additionally, Sutent (+1.1%), Tasigna (+0.7%), and Sprycel (+0.5%) acquired market share, whereas Tarceva lost the greatest share at −2.0%, followed by Nexavar at −1.0% and Tykerb at −0.4%. The remaining drugs in the class had modest share changes due to low volumes (

Figure 1


Demographics, Utilization, and Cost

According to the American Cancer Society, the estimated number of people diagnosed with cancer increased more than 21% between 2000 and 2009.1,2 More males were diagnosed than females both years. Males continue to have a higher ratio of new cases to death than females (

Table 2


The National Institutes of Health estimated 11 million Americans with a history of cancer were alive, either cancer free or still undergoing treatment in 2006.7 Males have a higher lifetime risk of developing some type of cancer (1 in 2 people) than females (1 in 3 people). The majority (77%) of cancers are diagnosed in persons age 55 years and older.1

eAppendix B

(available at

) provides the 2009 average percentage of total utilizers, utilization (as a percentage of total days supply), and total cost per utilizer for antineoplastic enzyme inhibitors by generation and gender. The Baby Boomers and Silent Generation represented more than 85% of the total utilizers.

The average annual total cost per utilizer was $21,722 for females and $24,459 for males. Combined, Baby Boomers and the Silent Generation accounted for 85.1% of the total spending for this class.

From 2008 to 2009, gross cost per day figures increased by 14%, led by Gleevec, which had a 14.7% increase to $129.48. Tarceva, Sutent, and Nexavar also had gross cost per day increases of 8.2%, 5.9%, and 13.7%, respectively (Figure 2). Tasigna (not shown in Figure 2) had the highest gross cost per day at $200.56, but claim volumes were comparatively low.

eAppendix C

(available at compares 2008 and 2009 utilization trends by both claims and days supply. Days supply varied by drug and was based on dosing (specifi c to cancer type) and patient demographics.


Antineoplastic enzyme inhibitors had a 19.0% gross trend, driven primarily by a 14.0% gross cost per day trend; utilization (days supply) increased 4.4% on a per member per month (PMPM) basis. Cost comparisons were not done because each drug in this class has a different purpose/subset of approved indications for a variety of conditions. However, the change for each drug was evaluated year over year. Only 1 of the primary drugs in this class, Tykerb, had a decrease (−4.2%) in gross cost per day in 2009. The remaining drugs had signifi cant year-over-year price inflation and contributed to the 14.0% year-over-year increase in gross cost per day driving the gross trend to 19.0%.

Gleevec had the largest increase in the number of prescription claims and a 4.8% increase in days supply PMPM. Nexavar lost the greatest number of claims and had a decrease of 10.2% in days supply PMPM. Gleevec utilization growth combined with a 14.7% gross cost per day increase acted as the primary driver of trend for the class, while Nexavar and Tarceva declines acted to moderate costs.

In November 2009, Votrient received approval from the FDA for advanced renal cell carcinoma. Uptake has been very low and metrics were not evaluated. Although many new development drugs are in the pipeline, there is no guarantee that the FDA will approve these drugs.


Although antineoplastic enzyme inhibitors are very costly and currently have no generic availability, these agents have greater tolerability and ease of administration (oral), and cause less intense reactions than many other cancer therapies. In addition, the aging of the Baby Boomers with their focus on wellness combined with early diagnosis likely will result in continued increases in the number of cancer cases being diagnosed and treated, therefore driving cost trends.