Real-World Utilization of Oral Anticancer Agents and Related Costs in Older Adults with Metastatic Renal Cell Carcinoma in the United States

Study population

This was a retrospective cohort study of SEER-Medicare patients diagnosed with mRCC from 2007–2015 who were enrolled in Medicare Part D for at least 1 year after diagnosis or until death (Fig. 1). Full cohort selection details are described in the Supplemental Appendix file. Patients were required to have at least 12 months of continuous enrollment in Medicare fee-for-service parts A and B before the SEER RCC diagnosis, and for Parts A, B, and D for 12 months after the metastatic index date or until death. Patients were excluded if their metastatic diagnosis occurred at autopsy or death, if they were < age 65 at metastatic index date, or if they had a second primary diagnosis of cancer at another site between the initial SEER RCC diagnosis date and their metastatic index date.

Fig. 1

Cohort inclusion and exclusion criteria diagram.

Patient characteristics

We examined patient and clinical characteristics including race/ethnicity, age at metastatic diagnosis, sex, stage at initial RCC diagnosis, histology at initial RCC diagnosis, marital status, geographic region of residence, metropolitan residence, and zip code socioeconomic characteristics. We used validated coding algorithms to assess patient comorbidities of interest in the 12 months prior to the metastatic index date using diagnosis codes (Supplemental Appendix B) from inpatient, outpatient, and carrier Medicare claims files [7, 8].

Use of oral anticancer agents

Utilization of an OAA was determined by a Part D prescription drug claim for any of the following OAAs that were FDA-approved by 2015: sorafenib, sunitinib, pazopanib, everolimus, and axitinib. Utilization was treated as a binary indicator if a patient filled a prescription in 12 months following the mRCC diagnosis.

Patient total, cancer-specific, and OAA-specific Medicare costs

Total Medicare costs in the year following diagnosis were obtained by summing line-item Medicare reimbursements from all outpatient, inpatient, home health, skilled nursing, durable medical equipment, hospice, and carrier claims for patients diagnosed with that cancer type over each calendar year. All Part D prescription reimbursement costs were calculated by subtracting the patient payment from the total cost for all Part D prescription claims in the evaluation period.

Cancer-specific costs were calculated from the subset of a patient’s claims that listed a primary RCC or metastatic cancer diagnosis code (ICD-9/ICD-10) or that had a procedure code for a cancer treatment procedure (Supplemental Appendix A). Part D cancer drug costs were calculated for the subset of a patient’s Part D claims for drugs approved to treat RCC.

OAA costs to Medicare were calculated by subtracting Medicare Part D patient payments from the total prescription claim cost for OAA prescription claims. Out-of-pocket costs for OAAs were defined as the patient payment amounts on OAA prescription claims. Costs were calculated for the patient’s first fill standardized to a 30 day supply, and summed for all of their fills in the 12 months following metastatic diagnosis.

Statistical methods

We examined differences in patient and clinical characteristics by receipt of OAA, year, and drug over time. Continuous variables were described using mean (SD) or median (IQR). Categorical variables were described using frequencies and percentages. Group differences were tested using t-tests and Cochran-Mantel-Haenszel tests for nonzero correlation. For each OAA of interest, we calculated the percentage receiving an OAA within the 12 months following their metastatic diagnosis. Univariable and multivariable log-binomial regression analyses were used to assess patient characteristics associated with OAA utilization within 12 months of metastatic diagnosis.

Costs were adjusted to 2015 dollars using the Consumer Price Index Medical Care component. Associations between costs and receipt of an OAA with adjustment for patient race, demographics, clinical characteristics, and year of metastatic diagnosis were modeled using multivariable generalized linear modeling with a gamma distribution and log-link. Multivariable models were also adjusted for a patient’s total Medicare costs, per $1000, in the baseline year before diagnosis to provide adjustment for baseline healthcare costs.

For patients who received an OAA, cost to Medicare and out of pocket costs for the patient’s first OAA fill standardized to a 30 day supply, and their total 12-month Medicare and out of pocket costs for OAAs were modeled using generalized linear modeling with a gamma distribution and log link with adjustment for patient race, demographics, clinical characteristics, and year of metastatic diagnosis.

Study approval

This study was approved by the Duke University Institutional Review Board (Protocol # Pro00101962).

Study population

Our study cohort included 2,792 patients with mRCC diagnosed from 2008–2015 (Table 1). The majority had an initial diagnosis of Stage 4 cancer (71.2%), while the remainder of the cohort’s RCC were initially diagnosed at a lower stage (Table 1). 76.2%of patients were of non-Hispanic white race (N = 2,103), 7%were non-Hispanic black race (N = 195), 10.8%were identified as Hispanic (N = 302), with 192 remaining patients of other races (Table 1). Black and Hispanic patients in the study were more likely to live in zip codes with higher poverty rates and lower educational attainment than white patients, and black patients were nearly half as likely as patients of other races to be married (Table 1). Black patients were less likely to have clear cell histology than other patients, and had higher rates of multiple comorbidities at diagnosis including hypertension, congestive heart failure, COPD, diabetes, end stage renal disease, and peripheral vascular disease (Table 1).

OAA utilization in metastatic RCC

Thirty-two percent of patients filled an OAA prescription in the 12 months following their mRCC diagnosis (Table 2). Between 50–60%of the cohort did not receive any systemic therapy in the 12 months following their diagnosis, with slightly higher rates of systemic treatment receipt in later study years (Supplemental Figure 1). OAAs were the most commonly used drug class for patients receiving therapy. Rates of OAA utilization in the mRCC cohort increased from 2007 (31%of patients) to 2015 (37%, trend p value < 0.001) (Fig. 2, Table 2). Sunitinib and pazopanib accounted for the majority of OAA use (Fig. 2). Among patients who received at least one OAA prescription, 57.6%received sunitinib as their first OAA, and 27.8%percent received pazopanib (Supplemental Table 1). Black Non-Hispanic patients had the lowest rate of OAA use compared to patients of other races (25%of black patients receiving OAAs vs 31%of Non-Hispanic rates patients, p value < 0.001, Table 2). The median time from diagnosis of mRCC to receipt of an OAA was 49 days (IQR 24–103 days); time to OAA receipt was shorter in patients with dual enrollment in Medicaid (–14 days, SE 3.04, p < 0.001) but did not differ by any other examined patient characteristics.

Fig. 2

Trends in receipt of oral anticancer agents in the 12 months following diagnosis with metastatic renal cell carcinoma among SEER-Medicare patients aged 65 and older.

After multivariable adjustment (Table 3), patient age at diagnosis, stage at initial cancer diagnosis, tumor histology, geographic region of residence, and certain comorbidities were associated with a patient’s likelihood of OAA receipt. Patients over age 81 years were half as likely to receive an OAA (RR 0.50 95%CI 0.42–0.60) compared to patients aged 66–70 years at diagnosis. Clear cell histology (RR 1.65 95%CI 1.38–1.98) and being stage 3 cancer at initial SEER diagnosis (RR 1.18 95%CI 1.01–1.37) were associated with higher likelihood of receiving OAAs, while patients initially diagnosed at Stage 1 were less likely to receive an OAA (RR 0.80 95%CI 0.65–0.98). Patients living in the Southern US were less likely to receive an OAA compared to patients living in the West (RR 0.83 95%CI 0.70–0.98), and patients who were married were 13%more likely to receive an OAA than unmarried patients (RR 1.13 95%CI 1.01–1.27). Patients with hypertension were more likely to receive an OAA (RR 1.32 95%CI 1.11–1.57), whereas patients with dementia were less than half as likely to receive an OAA (0.44 95%CI 0.26–0.74). Black patients had nominally lower relative risk of OAA utilization compared to white patients, but the association was not statistically significant in multivariable-adjusted models (RR 0.88 95%CI 0.68–1.15). When modeled with an interaction term for geographic region of residence and race, the interaction term was not statistically significant, indicating there was no evidence for the association between patient race and OAA utilization differing across geographic regions. There was also no evidence of interaction between zip code-level measures of SES and geographic region.

OAA utilization and total and cancer-specific healthcare spending

In multivariable-adjusted models, receipt of an OAA was associated with 36%higher total Medicare spending in the 12 months following metastatic diagnosis (RCR 1.36 95%CI 1.28–1.45), and 47%higher cancer-specific spending (RCR 1.47 95%CI 1.34–1.61) compared to no OAA receipt (Table 4). Hispanic race was associated with approximately 20%higher total costs (RCR 1.19 95%CI 1.06–1.33) and cancer-specific costs (RCR 1.20 95%CI 1.01–1.41), even after adjusting for receipt of an OAA. There was no difference in inpatient admission cost by race. When modeled with an interaction term for geographic region of residence and race, the interaction term was not statistically significant, indicating there was no evidence for the association between patient race and costs differing across geographic regions.

OAA-specific spending

Among patients who received an OAA in the 12 months following their metastatic cancer diagnosis (Table 5, N = 907), multivariable-adjusted per-patient Medicare spending on both the first OAA prescription and total spending on OAAs for mRCC in the 12 months following metastatic diagnosis increased 6%per year beyond inflation from 2008–2015 (Initial prescription cost standardized to a 30 day supply to Medicare: RCR 1.06 95%CI 1.04–1.08; Total OAA cost to Medicare: RCR 1.06 95%CI 1.05–1.08;). Conversely, patient out-of-pocket spending for the initial prescription (Fig. 3) and total 12-month patient out-of-pocket spending on OAAs decreased approximately 9-10%per year (initial OOP prescription cost standardized to a 30 day supply: RCR 0.91 95%CI 0.88–0.95; total 12 month OAA cost to patient: RCR 0.90 95%CI 0.86–0.93). 9.2%of patients had zero out-of-pocket costs for their OAA fill; the distribution of out of pocket costs paid by patients for a 30 day supply shifted downward for each drug type from 2007–2015, though in 2015 more than half of patients were still paying > $1000 out of pocket for a thirty day supply. Medicare spending on both the first OAA fill and spending over 12 months was consistently lower for patients receiving pazopanib or sorafenib at their first fill compared to patients who initially received sunitinib. Patient out-of-pocket costs were 23%lower for patients receiving pazopanib at their first prescription and more than three times higher for patients receiving everolimus compared to patients who received sunitinb (Table 5). Out-of-pocket spending for both the first prescription fill standardized to a 30 day supply and over 12 months were consistently lower in patients of black, Hispanic, or other races compared to Non-Hispanic White patients; however, spending on OAAs by Medicare for the index fill and over 12 months did not differ across patient race/ethnicity categories (Table 5).

Fig. 3

Distributions of out of pocket costs and costs to Medicare: inflation-adjusted and standardized to a 30 day supply for patient’ first OAA prescription by diagnosis year.