Trends in Utilization, Prices, and Spending for Oral Medications for Breast Cancer Treatment in the US Medicaid Population, 2008-2019

The Centers for Disease Control and Prevention defines breast cancer as “a disease in which cells in the breast grow out of control.”¹ Several types of breast cancer have been characterized, and each type depends on the cells in the breast tissues that turn into cancer.¹ In the early stages of breast cancer, no symptoms are typically noted, and it is usually detected by either self-examination or mammography screening.² In a study by Roth and colleagues, a large percentage (39%) of breast cancers were detected by the women themselves.² The investigators described the characteristics of 361 female breast cancer survivors in the United States who were diagnosed between 1980 and 2003 and the time trends for several methods of breast cancer detection using the 2003 National Health Interview Survey.² They concluded that a majority (57%) of breast cancer survivors reported a breast cancer detection method other than mammography. Women often detected breast cancer themselves by accident (18%) or by self-examination (25%).²

The most common symptom of breast cancer is a painless lump or mass in the breast tissue.³ Some people do not have any signs or symptoms of breast cancer, although warning signs for breast cancer have been identified, such as changes to the breast skin (thickening, swelling, or redness) and nipple abnormalities, such as spontaneous discharge (particularly if it is bloody).³

According to the American Cancer Society (ACS), estimates for women in the United States in 2022 were 287,850 newly diagnosed cases of invasive breast cancer and 43,250 deaths from breast cancer.³ The ACS has estimated that 1 of 8 women in the United States will have invasive breast cancer in their lifetime.³ Furthermore, the annual incidence of breast cancer has increased from 2015 to 2019 by 0.7% in Black women and by 0.5% in White women.³ Although breast cancer is the leading cause of US cancer-related death in Black women and the second leading cause of US cancer-related death in White women, the US death rate from breast cancer from 2011 to 2020 decreased to 1.3% annually.³ This reduction can be explained by the availability of advanced treatments, the early detection of breast cancer by mammography screenings, and increased awareness of breast cancer.³

According to the American Society of Clinical Oncology, the average monthly cost of newly approved cancer medications is more than $10,000. Moreover, although breast cancer clinical outcomes in the United States are similar to those in other countries, the US cost is more than twice as high.⁴ This high cost may not be affordable even for insured patients. Ekwueme and colleagues analyzed Medicaid Analytic eXtract claims and enrollment data from 2007 and concluded that the high cost of oral drugs for the treatment of breast cancer threatens the affordability of cancer care.⁵ For long-term survival, access to treatment for breast cancer is crucial. Nevertheless, breast cancer treatment costs can impose a significant financial burden, especially for younger women and those of low social economic status.⁵

In addition, access to treatment and financial burdens can be challenging for patients with Medicaid, even though Medicaid recipients do not have to be liable for the costs for treatments.⁵ Conti and colleagues conducted a study on the national spending trends on 47 oral cancer treatments between the first quarter of 2006 and the third quarter of 2011.⁶ The study’s results showed that although spending decreased on oral cancer treatments that had lost their patent protection, including hormone therapies for breast cancer, their use increased.⁶

Campbell and Ramsey reviewed studies of the treatment cost of breast cancer in the United States and concluded that the lifetime cost per patient ranged between $20,000 and $100,000 and that chemotherapy was the greatest driver of the total direct cost.⁷ In addition, another study assessed the cost and use of resources in women with breast cancer in the United States.⁸ This study showed that the mean monthly cost per patient was $2896, which was driven primarily by costs attributable to hospitalization, pharmacotherapy, and surgical intervention.⁸ Moreover, among all cancers, breast cancer has the highest treatment cost.⁹ In the United States, approximately 13% of all cancer treatment costs are for breast cancer.⁹ Moreover, in 2010, the cost of treatments for breast cancer was approximately $16.5 billion in the United States, and this amount was expected to increase to $20.5 billion by 2020.¹⁰ Furthermore, according to a 2015 study, the total annual cost of metastatic breast cancer in the United States would increase to $152.4 billion in 2030, a 140% increase compared with $63.4 billion in 2015.¹¹

In the United States, treatments for breast metastases are a major contributor to the total cost of breast cancer.⁶ In a study by Rao and colleagues, the mean total cost of treatment for a patient with metastatic breast cancer was almost 9-fold greater than for a patient without cancer.¹² Internationally, a Swedish study investigated the treatment cost for breast cancer in various stages in clinical practice.¹³ The study showed that an increase in disease stage was associated with an increase in resource use and cost. The estimated annual total cost for patients with metastatic breast cancer who were aged <65 years was $46,500.^13,14

In the current literature, few studies examine the cost of breast cancer treatments in the Medicaid population. Also, most of the available evidence focuses more on the economic burdens of screening and healthcare services. To our knowledge, no studies have examined the utilization, expenditure, and patterns of oral treatments for breast cancer among the Medicaid population. Therefore, the objective of this study was to assess the trends in utilization, reimbursement, and cost per prescription of brand-name and generic oral drugs for the treatment of breast cancer in the US Medicaid population during the 12 years from 2008 to 2019. By addressing this knowledge gap, this study aims to help payers, healthcare providers, and policymakers develop strategies that optimize the allocation of resources and patient access to medication for this population.

Methods

In this retrospective drug utilization study, we examined pharmacy data during the study period of 2008 to 2019 from the national Medicaid drug utilization files provided by the Centers for Medicare & Medicaid Services (CMS). These files contain information about the numbers of prescriptions and total Medicaid payments to pharmacies for individual drugs. CMS collects these data from US states for use in the federal Medicaid Drug Rebate Program, and they are updated on a quarterly basis. The database includes Medicaid beneficiaries from 50 states and the District of Columbia and is restricted to pharmaceutical drugs prescribed on an outpatient basis.¹⁵ The CMS data were collected for individual National Drug Code (NDC) drug forms. The National Summary Files were compiled by aggregating data across the state databases. Each data record in the database included the NDC, drug name (brand or generic), year and quarter of the Medicaid expenditure, number of prescriptions, number of units (eg, individual capsules or tablets), and the total pharmacy reimbursement amount, including the costs of the medication and its dispensing fee (ie, the administrative fee). The first 5 digits of the NDC number identify the drug manufacturer, and the remaining digits identify the specific drug by strength, dose formulation, and packaging.¹⁶

We searched each of the drugs listed in Table 1 using NDC codes. All oral drugs for the treatment of breast cancer were included in our study. For each drug, the annual number of prescriptions and the annual reimbursement amount were calculated separately, then the annual total was aggregated. In the data set, the price per prescription is not accessible; therefore, we estimated the cost per prescription for each of the drugs by dividing the reimbursement amount by the total number of prescriptions. Although per-prescription reimbursement may not be the ideal measure, this traditional estimation approach for price has been extensively used by researchers studying the Medicaid program and its expenses using the same data source.^17-22

All expenditure values in the study are expressed in US dollars. Descriptive statistics were used to analyze the trends in the prescription counts, the total reimbursement amount, and the cost per prescription over the 12-year study period. All data analyses were conducted using Statistical Analysis Software version 9.4 (SAS Institute Inc; Cary, NC). Excel 2017 (Microsoft Corporation; Redmond, WA) was used to further develop the data.

Results

Table 2 shows the total number of prescriptions of oral generic breast cancer drugs and Table 3 shows the total spending over time. In general, the number of prescriptions increased by 764.21% from 68,213 in 2008 to 589,506 in 2019. In addition, if the annual change was compared by year, the greatest percent increase was observed in 2011 when the total number of generic prescriptions increased by 153.97% compared with 2010. Over the study period, prescription counts declined in some years; the greatest decrease was observed in 2016 when the number of prescriptions decreased by 27.74%.

From 2008 to 2019, the total annual spending increased by almost 1831%, from $2.2 million in 2008 to $43 million in 2019. The greatest percent increase in spending was observed in 2014 (242.22%). A decrease in the spending percentage was seen in some years; the largest percent decrease was in 2017 (28.2%; Table 3).

The trends of the total numbers of prescriptions for each oral generic breast cancer drug are shown in Figure 1 and Table 2. From 2008 through 2016, the number of prescriptions of tamoxifen increased by 203% followed by slight decreases from 2017 through 2019. For capecitabine, the prescription counts increased from 19,008 in 2014 to 34,633 in 2019, a percent increase of approximately 82%. Through the study period, toremifene was only used in 2019, and the prescription count was only 213. Toremifene was also used before 2008. From 2010 to 2015, the number of anastrozole prescriptions increased by 516%, followed by a sharp decrease in 2016 to 2017 (72% decrease). After 2017, the number of prescriptions sharply increased from 48,876 in 2017 to 226,852 in 2019 (364% increase).

For the remaining generic drugs, (ie, exemestane, letrozole), significant percent increases were seen in the prescription counts from 2017 to 2019, 631% for exemestane and 364% for letrozole.

For all generic drugs in the study, the patterns of reimbursement and spending are shown in Figure 2 and Table 3. For tamoxifen, the total reimbursement amount increased from $2,227,150 in 2008 to $5,084,068 in 2015 (an increase of 128%). From 2015 to 2019, this increase was followed by a 31% decrease, to $3,462,987. Capecitabine was the generic drug with the highest total reimbursement amount, which peaked in 2015 with a total reimbursement amount of $68,247,835, followed by a sharp decline that continued until 2019. For exemestane, spending increased from 2011 to 2015, then sharply decreased in 2017 and increased again in 2018. There was a decline in spending on anastrozole and letrozole in 2016 and 2017.

In general, the cost per prescription of generic drugs decreased between 2008 and 2019, as shown in Figure 3 and Table 4. For example, from 2014 to 2019, the cost of capecitabine decreased by 61%, from $2297 to $875. None of the generic drugs in this study had an increase in cost during the study period.

For brand-name drugs, the numbers of prescriptions as well as the total spending over time are shown in Table 5. The number of prescriptions decreased by 59% from 143,009 in 2008 to 58,272 in 2019. Looking at the annual change, the greatest percent increase was observed in 2016, when the prescription count increased by 35% compared with 2015. Like the generic drugs, there was a decrease in the prescription counts in some years, and the largest percent decrease (by 45%) was in 2012.

Conversely, the total annual spending increased by 819% from approximately $72.5 million in 2008 to $666.3 million in 2019. The greatest percent increase in the prescription count was in 2016, and therefore the largest percent increase in spending (approximately 70%) was in 2016 as well.

For each brand-name drug in the study, the total number of annual prescriptions are shown in Table 6 and Figure 1. During the study period, the number of prescriptions of Xeloda increased by 64% from 2008 to 2012; however, this number dramatically decreased by 82% during the period of 2013 to 2017. Between 2009 and 2019, the use of Afinitor increased by 4409%, from a prescription count of 272 in 2009 to 12,265 in 2019. In addition, Kisqali was introduced in 2017, and its use increased (by 534%) rapidly, from 446 prescriptions in 2017 to 2827 prescriptions in 2019.

Correspondingly, the number of prescriptions of Lynparza, which was approved in December 2014, increased by 584% from 580 prescriptions in 2015 to 3967 prescriptions in 2019. Moreover, there was a rapid increase in the use of Verzenio, which was approved in 2017, from 62 in 2017 to 3933 in 2019 (an increase of 6244%). The number of prescriptions of Tykerb increased from 2008 to 2012 by 58%. Conversely, during the study period, the number of prescriptions of Aromasin decreased by 99%, from 11,713 prescriptions in 2008 to 122 prescriptions in 2019. Similarly, the number of prescriptions of Arimidex decreased by more than 99% from 73,162 prescriptions in 2009 to 215 prescriptions in 2019. Moreover, the use of Ibrance increased every year since its entry to the market in 2015.

The patterns of reimbursement and spending for all brand-name drugs in our study are shown in Figure 2 and Table 7. Among the brand-name drugs, Ibrance had the highest total reimbursement, reaching $273,938,143 in 2018. Furthermore, the reimbursement of Afinitor increased the most in 2019, to $206,880,592. Within only 2 years (2017-2019), spending on Verzenio and Kisqali increased by 6562% and 612%, respectively. From 2015 through 2019, spending on Ibrance and Lynparza increased rapidly. Spending on Aromasin and Arimidex had an overall decrease during the study period.

The cost of most brand-name drugs in the study increased throughout the study period (2008-2019; Figure 3 and Table 8). For example, the cost of Afinitor increased by 219% from $5280 in 2009 to $16,868 in 2019. For Verzenio, there was a slight decline in cost, from $10,434 in 2017 to $10,231 in 2018. In addition, the cost of Lynparza increased by 95%, from $6127 in 2015 to $11,937 in 2019. Last, the cost of Fareston increased significantly by 710% from $162 in 2008 to $1312 in 2019.

Discussion

In this retrospective drug utilization study, during the 12-year study period the total count of Medicaid-reimbursed prescriptions for generic oral breast cancer drugs increased significantly, from 68,213 in 2008 to 589,506 in 2019, which is a 764.21% increase. Conversely, the total number of prescriptions of brand-name oral breast cancer therapies decreased by 59% from 143,009 in 2008 to 58,272 in 2019. This reduction might be attributed to the availability of generic versions of a drug and the expiration of patent protection for some drugs. Moreover, for generic drugs, several applications were usually approved by the FDA to market a single drug, and this creates more competition in the pharmaceutical marketplace and results in lower drug costs. Typically, when multiple generic drug companies market a single drug approved by the FDA, market competitions occur between pharmaceutical companies with prices that are approximately 85% less than the brand-name drug.²³ A report by the Association for Accessible Medicines states that the US healthcare system saved approximately $1.67 trillion from 2007 to 2016 from the use of generic drugs.²⁴ For example, in our analysis, the total number of brand-name prescriptions of Nolvadex decreased substantially. Nevertheless, the use of its generic version, tamoxifen, increased by 152% during our study period.

Generic capecitabine entered the market in 2013 and is an attractive option for the treatment of breast cancer in women because it does not cause hair loss, particularly as part of long-term treatment protocols.²⁵ Since the entry of capecitabine in the market, Medicaid’s expenditure on its brand-name version Xeloda decreased from $75 million in 2013 to $19.7 million in 2019 (Table 7). However, the price per prescription of Xeloda increased by 40% from 2013 to 2019 (Table 8). The reason behind this increase is that the brand-name drug manufacturer is trying to maximize its revenue.

Not all brand-name drugs were affected by the entry of generic drugs into the market. Some healthcare providers and patients are skeptical of the effectiveness and side-effect profiles of generic drugs and believe that brand-name drugs are of higher quality than generic drugs. So, they continue to use the brand-name drug even when generic versions are available.

In general, the cost per prescription for most of the brand-name medications in the study increased from 2008 to 2019. This increase in the costs of most oral drugs for breast cancer has been shown in a previous study by Shih and colleagues.²⁶ In addition, the trends in the current study are similar to trends in Medicaid utilization, spending, and pricing for other medication categories in previous studies, such as specialty drugs for migraine, bacterial infections, and multiple sclerosis.^27-29 Kelly and colleagues conducted a longitudinal drug utilization study and compared the pattern of use of tamoxifen and aromatase inhibitors among 9 developed countries.³⁰ The study showed that there was a shift from the use of tamoxifen to aromatase inhibitors, and the utilization patterns increased in most of the countries in their study.³⁰ According to our analysis, tamoxifen and its brand-name version Arimidex were the most frequently prescribed oral medications for the treatment of breast cancer among the Medicaid beneficiaries.

Our analysis showed that in 2017, a sharp decrease occurred in the use and reimbursement of generic aromatase inhibitors (anastrozole, letrozole, and exemestane). This decrease can be explained by the following reasons. First, in 2017, a trial showed that 2 years of extended therapy is sufficient for anastrozole instead of 5 years, so the decrease might be because some women stopped taking it after their physicians notified them of the trial’s results.³¹ Second, in 2017, Kisqali, the brand-name version of ribociclib, a protein kinase inhibitor, was approved for use in combination with letrozole; also in 2017, the FDA approved a co-pack that has both medications.^32,33 Finally, the original data set in our study had missing data in several quarters of 2017.

For the brand-name drugs Verzenio, Ibrance, Kisqali, and Nerlynx, currently no generic versions are available in the US pharmaceutical market. Therefore, we expect that the expenditures for these medications and the price per prescription will continue to increase for several years, especially because the patents of some of these medications are protected until 2030. In addition, Afinitor, which was first approved by the FDA in 2009, faced generic competition for specific doses in December 2019, and Novartis expected competition to increase because of this.^34-36 Consequently, the price and spending for Afinitor decreased once generic everolimus entered the market.³⁶

Limitations

The major strengths of this utilization study are the long study period, which covered 12 years from 2008 to 2019, and the large representative study group from the Medicaid population. Nevertheless, the current study had several limitations.

First, in this retrospective descriptive study we used data sets that lack patient-specific information. Therefore, we could not perform multivariate analysis to assess the impact of patient characteristics on utilization and spending trends or determine the appropriateness of breast cancer medication use in the Medicaid population.

Second, the generalizability of this study is limited to the Medicaid population, which is predominantly comprised of a low-income population, in particular women and children. Accordingly, our study findings may not represent the expenditure and utilization trends in other populations, such as privately insured patients.

Third, prescribers’ behaviors may impact prescription patterns. Some healthcare providers prefer one drug over another because of their clinical experience or their brand loyalty to certain pharmaceutical companies.³⁷ Therefore, prescriber behavior is considered a confounder that may bias our study’s results. Finally, the current study findings are limited by the available data in the CMS national Medicaid pharmacy files.

Conclusion

Our study showed the presence of competition between generic and brand-name oral medications for breast cancer in the US pharmaceutical market. For Medicaid policymakers, this study provides enlightening data about the increasing cost trends of drugs for breast cancer. We anticipate that our study’s findings will encourage and inspire policymakers to investigate new approaches to control increased spending on drugs for breast cancer.

Several cost-containment strategies could decrease the cost of medications, such as implementing drug utilization review programs, increasing cost-sharing or co-payments, initiating medication therapy management programs, and instituting mandatory generic substitution. Furthermore, our findings allow healthcare providers to consider affordability when prescribing oral medications for breast cancer to enable patient access to medication and hence improve clinical outcomes and optimize the use of the drugs. Our research highlights the need for the implementation of cost-containment strategies to control the economic burden of therapies for breast cancer on the Medicaid budget.

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