Cost of Home vs Clinic Administration of Paclitaxel in Metastatic Breast Cancer

ABSTRACT

Objectives: To estimate the costs associated with home administration of oral paclitaxel and encequidar (novel P-glycoprotein pump inhibitor allowing oral paclitaxel bioavailability) compared with clinic/office administration of intravenous (IV) paclitaxel (175 mg/m²) and protein-bound paclitaxel in US patients with metastatic breast cancer.

Study Design: Economic analysis.

Methods: A cost calculator was constructed from a payer’s perspective including all costs related to administration of the chemotherapies, including drug administration, premedications and concomitant medications, oncologist office visits, laboratory testing, and administration-related adverse events. Total administration cost per patient per month (PPPM) and 6-month costs per patient were estimated for oral paclitaxel and encequidar, 175 mg/m2 IV paclitaxel, and protein-bound paclitaxel. Three scenarios for oral paclitaxel and encequidar, a weekly IV paclitaxel scenario (80-100 mg/m²), and univariate sensitivity analyses were conducted.

Results: Home administration of oral paclitaxel and encequidar was associated with a total administration cost of $523 PPPM, 64.4% lower than once-every-3-weeks IV paclitaxel (175 mg/m²; $1469 PPPM) and 63.8% lower than protein-bound paclitaxel (260 mg/m²; $1445 PPPM). Difference in costs was driven largely by higher administration and premedication costs associated with IV therapies. Scenario analyses showed that increased clinical experience with home administration of oral paclitaxel and encequidar was associated with reduction in cost of care associated with its administration over time. For the weekly IV (80-100 mg/m²) paclitaxel scenario, the total administration cost was $2510 PPPM (4.8 times higher than for oral paclitaxel and encequidar). Univariate sensitivity analysis demonstrated that the model findings were robust.

Conclusions: Home administration of oral paclitaxel and encequidar was associated with lower administration costs compared with once-every-3-weeks IV paclitaxel (175 mg/m²) and protein-bound paclitaxel, resulting in potential cost savings for payers.

Am J Manag Care. 2021;27(Spec 2). Published online December 24, 2020. https://doi.org/10.37765/ajmc.2021.88563

TAKEAWAY POINTS

Home administration of oral paclitaxel and encequidar was associated with a total administration cost of $523 per patient per month (PPPM), 64.4% lower than intravenous (IV) administration of paclitaxel (175 mg/m2; $1469 PPPM) and 63.8% lower than protein-bound paclitaxel (260 mg/m2; $1445 PPPM) in patients with metastatic breast cancer.

• Conventional cytotoxic IV chemotherapies require substantial resources at the place of infusion and are associated with severe toxicities.

• Encequidar, a highly selective P-glycoprotein inhibitor, allows absorption of oral paclitaxel into the bloodstream, thereby eliminating infusion-related adverse effects.

• Findings from this study indicate that home administration of oral paclitaxel and encequidar may result in cost savings for payers.

INTRODUCTION

According to National Comprehensive Cancer Network guidelines, sequential single-agent cytotoxic chemotherapy, such as paclitaxel or protein-bound paclitaxel, is recommended for recurrent or metastatic breast cancer (mBC).¹ For patients with incurable malignancies, when oral drugs’ efficacy and adverse effect (AE) profiles are comparable with those of intravenous (IV) options, the oral drugs are perceived to afford a greater quality of life.2 Benefits of oral administration may include patient convenience and reduction of discomfort due to avoidance of hospital and infusion center visits for invasive drug administration. Avoidance of IV drug administration eliminates the risk of infusion reactions and the need for premedication with agents such as steroids and antihistamines.^3,4 In addition, oral chemotherapy might be associated with cost savings, given that less time is required in clinic because of home administration.⁵ Among IV and oral chemotherapies of similar efficacy, surveys have shown that most patients would prefer oral over IV chemotherapy.^2,6

To date, oral formulations of agents such as paclitaxel have not been possible because of poor absorption into the bloodstream as a result of the active excretion by P-glycoprotein (P-gp). P-gp is an active efflux pump that prevents the absorption of substrates (such as taxanes) across the intestinal epithelium into the systemic circulation.⁷ Encequidar is an investigational, potent, highly selective P-gp inhibitor that blocks intestinal P-gp, allowing for better absorption of oral paclitaxel into the bloodstream, thereby eliminating the infusion-related AEs associated with IV paclitaxel.⁸ Oral paclitaxel and encequidar is the first oral taxane plus P-gp inhibitor that demonstrated a significant improvement in confirmed overall response rate and overall survival compared with IV paclitaxel in findings from its phase 3 trial. Compared with IV paclitaxel, this oral therapy was also associated with a lower risk of neuropathy and alopecia but a higher incidence of hematologic and gastrointestinal AEs.⁸

The objective of this study was to estimate the costs associated with home administration of oral paclitaxel and encequidar compared with clinic/office administration of IV paclitaxel (175 mg/m²) and protein-bound paclitaxel from a US payer perspective in patients with mBC.

METHODS

Model Structure and Assumptions
A Microsoft Excel–based cost-calculator model was constructed from a US payer perspective to calculate aggregated costs associated with home administration of oral therapy vs clinic/office administration of IV therapy over a 6-month treatment duration (Figure 1).

The target population for this model included patients with mBC with any receptor status. For the base case analysis, a health plan with 10,000 treated patients with mBC was assumed, with 30% assumed to have Medicare insurance. The model evaluates patients starting on the following treatments:

• (A) ORAL PACLITAXEL AND ENCEQUIDAR: home administration (both medications are taken once daily for 3 consecutive days each week)
• (B) IV PACLITAXEL (175 MG/M²): office/clinic infusion (once every 3 weeks)
• (C) PROTEIN-BOUND PACLITAXEL (260 MG/M²): office/clinic infusion (once every 3 weeks)

The cost-calculator model included all direct costs (pertaining to payers) related to administration of the oral or IV therapies; these included drug administration (drug preparation and equipment, supplies and resources required for administration), premedications and concomitant medications, oncologist office visits, laboratory testing, and administration-related AEs. Administration-related costs included any costs associated with the administration, including use of local anesthesia; IV access; access to indwelling IV, subcutaneous catheter, or port; flush at conclusion of infusion; standard tubing, syringes, and supplies; and preparation of chemotherapy agent.⁹ Laboratory testing included routine tests conducted alongside chemotherapy, including complete blood count (CBC) and comprehensive metabolic panel (CMP). Only AEs of grade 3 or 4 directly related to administration route (oral and IV) were included in the model (ie, allergic and injection site/infusion reactions, nausea/vomiting, diarrhea).

Assumptions
The model considers only outcomes and costs that are associated with the specific route and setting of administration of each drug therapy, including severe administration-related AEs (ie, grade 3 or 4). Since the focus of the study was to estimate costs associated with administration only, the drug costs of encequidar, oral paclitaxel, IV paclitaxel, and protein-bound paclitaxel were not included in the analysis. The drug-specific clinical efficacy (eg, overall survival) and AEs (other than administration-related) were considered equal and were not included in this analysis. All patients were assumed to be on chemotherapy for the entire 6 months with 100% adherence to medication and office visit and lab testing schedules. To make comparisons uniform, each month was assumed to be composed of 28 days, and all therapies were assumed to have started on week 1 of the first month.

Data Sources and Input Parameters

Table 1 summarizes the input parameters and data sources included in the model. The model was populated with data from 3 primary sources: a targeted review of the peer-reviewed literature, the preliminary AE rates of oral paclitaxel and encequidar from the phase 3 clinical trial,⁸ and expert oncologist opinion. Three breast cancer oncologists (experts) based in large academic institutions in different US geographic locations, with a mean of 8 to 10 years of clinical practice experience, were interviewed to obtain their opinions on practice patterns with IV and oral therapies in patients with mBC. Specifically, the interviews aimed to capture data about: (1) drug administration schedule, including premedications; (2) the frequency of oncologist visits, home nurse visits, and lab testing; (3) premedications; (4) monitoring of patients for AEs; and (5) administration-related AE risk. Two rounds of teleconference panel sessions were conducted with the experts to obtain data. The first session with each expert was a 1:1 interview, and the second interview session was a group interview that involved discussion of previous answers to reach consensus among the experts.

RESOURCE UTILIZATION. For oral paclitaxel and encequidar, base case analysis data for frequency of oncologist office visits and lab testing were obtained from expert interviews. The dosing schedule for oral paclitaxel and encequidar was provided by Athenex’s product information. For IV paclitaxel (175 mg/m²) and protein-bound paclitaxel, frequency of IV administration was captured from their package inserts.^10,11 Frequency of oncologist visits and lab testing for IV therapies was derived from expert opinion.

COSTS. For all therapies, cost of an oncologist visit was derived from the 2020 CMS Physician Fee Schedule.12 Medicare costs for lab testing (CBC and CMP) were derived from the 2020 Clinical Laboratory Fee Schedule. Commercial/private insurer costs for lab testing were based on mean commercial reimbursement amounts obtained from laboratory pricing and reimbursement data available from Sparrow Health System.^13,14

Cost for premedication (the antiemetic ondansetron) for oral paclitaxel and encequidar was estimated from 2020 Average Sales Pricing data from CMS.¹⁵ For IV and protein-bound paclitaxel, administration and premedication/concomitant medication costs were estimated from a retrospective database study evaluating the cost components for administering a single-agent IV breast cancer drug to women with mBC in the United States.¹⁶ Based on the distribution of individual components in mean cost per IV-administration visit, costs for administration and premedication/concomitant medications were estimated for IV paclitaxel and protein-bound paclitaxel. Premedications/concomitant medications for IV therapies included antiemetic agents (eg, palonosetron, granisetron), saline solution, dextrose water, corticosteroids (eg, dexamethasone), heparin, antihistamine (eg, diphenhydramine), and histamine-2 receptor antagonists (eg, ranitidine).

Only those AEs of grade 3 or 4 that were related to the specific route of administration were included in the model (ie, allergic and injection site/infusion reactions, nausea/vomiting, diarrhea). The rates of grade 3 or 4 AEs were based on preliminary phase 3 clinical trial data for oral paclitaxel and encequidar,⁸ package inserts for IV and protein-bound paclitaxel, and expert opinion.^10,11 Administration-related AE costs per event were derived from an oncology budget impact study. This study estimated costs of managing AEs (grade 3 or 4) by identifying each AE with specific diagnosis codes and associated resource use and costs from the Healthcare Cost and Utilization Project data.¹⁷

Outcomes and Analysis
Outcomes were assessed over a 6-month treatment duration. The primary outcomes of the model were the total costs associated with home administration of oral paclitaxel and encequidar and clinic/office administration of IV paclitaxel (175 mg/m²) and protein-bound paclitaxel per patient per month, as well as 6-month costs per patient. The outcomes were calculated for the entire duration of treatment by summing all individual component costs. All costs were inflated to 2019 US dollars using the Medical Care Consumer Price Index.¹⁸

In addition, three scenario analyses were conducted for oral paclitaxel and encequidar to evaluate the impact of varying key clinical inputs on the cost of administration. These scenarios modeled varying frequencies of oncologist office visits and lab testing to demonstrate the impact on cost of home administration once oncologists gained experience with the new regimen. They were (1) decreased frequency of lab testing after 3 months of treatment initiation, (2) decreased frequency of lab testing after cy of oncologist visits and lab testing after 1 month of treatment initiation.

In this cost analysis, IV paclitaxel (175 mg/m²), the FDA-approved dose of IV paclitaxel for the treatment of mBC that is given every 3 weeks, was included to maintain consistency with the phase 3 trial of oral paclitaxel and encequidar. However, an additional “weekly IV paclitaxel” scenario was conducted in which weekly IV paclitaxel (80-100 mg/m2) was included as an alternative regimen because it is another dosage of IV paclitaxel commonly used in clinical practice for the treatment of mBC.

Univariate sensitivity analyses were conducted to determine the extent to which uncertainty inherent to the model inputs affected the modeled outcomes when the inputs were varied 1 at a time. The high and low values of clinical inputs for oral paclitaxel and encequidar (such as oncologist visits and lab testing frequencies) were based on clinical relevance determined by experts or literature. Clinical meaningfulness pertains to minimum or maximum number of oncologist/lab visits that would be required based on clinical experience, so rather than varying these variables by 30%, clinically relevant values were selected.

All other inputs were varied to 30% higher and 30% lower than the base case values to analyze the impact on results. Oncologist visits and lab testing frequencies of IV therapies were not varied in the sensitivity analyses, as schedules for those dosing regimens are well established.

RESULTS

Base Case
The results of the base case analysis are shown in Table 2. The base case analyzed the per-patient per-month (PPPM) cost of home administration of oral paclitaxel and encequidar compared with clinic/office administration of IV paclitaxel (175 mg/m²) and protein-bound paclitaxel for a treatment duration of 6 months for 10,000 patients with mBC with 30% of patients covered by Medicare.

The total administration costs for oral paclitaxel and encequidar, IV paclitaxel (175 mg/m²), and protein-bound paclitaxel were $523 PPPM, $1469 PPPM (2.8 times higher than oral paclitaxel and encequidar), and $1445 PPPM (2.8 times higher than oral paclitaxel and encequidar), respectively. The difference in costs was driven largely by higher costs for administration and for premedication associated with IV therapies. The total administration cost PPPM for oral paclitaxel and encequidar was 64.4% lower than for IV paclitaxel (175 mg/m2) and 63.8% lower than for protein-bound paclitaxel.

Scenario Analysis
The results of the scenario analyses are shown in Table 3. The 3 scenario analyses showed that with decreasing frequency of oncology office visits and lab tests, as oncologists gained more experience with the home administration of oral paclitaxel and encequidar, 7% to 28% reductions of the cost of care associated with its administration would occur in the base case analysis. For the weekly IV paclitaxel scenario, the total administration cost for weekly IV paclitaxel (80-100 mg/m2) was $2510 PPPM (4.8 times higher than oral paclitaxel and encequidar).

Sensitivity Analysis
Detailed results of the 1-way sensitivity analysis are shown in Supplementary Table 1. Figure 2 shows the input variables that resulted in maximum variability in home administration of oral paclitaxel and encequidar cost PPPM. Cost (PPPM) of home administration of oral paclitaxel and encequidar varied the most when the frequency and cost of oncologist office visits, frequency of CBC lab visits, and incidence and cost of nausea/vomiting were increased or decreased by approximately 30%. By varying each model input 1 at a time, the cost of home administration of oral paclitaxel and encequidar increased by a maximum of $68 PPPM compared with the base case analysis, indicating that the model was robust.

DISCUSSION

In oncology, including mBC, cytotoxic chemotherapy is primarily administered IV rather than orally.¹⁹ The advantages of oral chemotherapy could be multifold. Compared with IV chemotherapy, it provides ease of administration with respect to timing and location (ie, home setting). Oral chemotherapy also has the potential to provide relatively prolonged treatment exposure as compared with IV infusions. Use of oral chemotherapy can potentially result in reduced health care resource utilization of outpatient infusion-related services. Overall, oral therapy could result in better quality of life than parenteral administration.²⁰ However, oral administration of many anticancer agents, including paclitaxel, has not been possible due to poor absorption into the bloodstream due to the active excretion by P‑gp in the intestinal cells.⁷ Studies have shown that when administered with encequidar, a highly specific intestinal P-gp inhibitor, oral paclitaxel achieves therapeutic blood levels and is more efficacious than IV paclitaxel in patients with mBC.^4,8

In the current study, a cost calculator model demonstrated that, from a US payer perspective, home administration of oral paclitaxel and encequidar was associated with much lower total administration cost PPPM than clinic/office administration of IV paclitaxel (175 mg/m²) and proteinbound paclitaxel, assuming equal efficacy and safety other than administration-related AEs. Findings show that home administration of oral paclitaxel and encequidar may result in potential cost savings for payers. The immediate cost savings associated with oral paclitaxel and encequidar from the payer’s perspective for a 6-month treatment duration were approximately $940 PPPM compared with IV chemotherapies. The key drivers of cost savings were found to be the lower administration costs and the much lower premedication costs associated with home administration of oral therapy.

The findings from this study are consistent with those of other pharmacoeconomic studies that compared costs associated with oral vs IV chemotherapies. Cassidy et al conducted a cost-effectiveness study of oral capecitabine and IV 5-fluorouracil/leucovorin (5-FU/LV) in patients with Dukes’ C colon cancer, wherein incremental direct costs (ie, chemotherapy, treatment administration visits, hospitalization, and management of AEs) and societal costs (ie, time and travel) were assessed. ²¹

The study results showed that compared with 5-FU/LV, capecitabine was the dominant treatment: It was associated with almost half of the direct costs (£3176 vs £6829), one-fifth of the societal costs (£381 vs £1699), and better outcomes. Although capecitabine had higher acquisition costs, its associated costs for administration, management of AEs, and patient travel and time were much lower than those of 5-FU/LV.21 Similarly, Lay et al conducted a cost minimization analysis (assuming equal efficacy) of oral vinorelbine and IV chemotherapies (vinorelbine, gemcitabine, paclitaxel, and docetaxel) for treatment of patients with non–small cell lung cancer. They found that IV chemotherapies were associated with costs per patient that were 1.2 to 2.3 times higher than those of oral vinorelbine (£3746, £5332, £5977,and £6766, respectively, vs £2888).²²

Strengths and Limitations

Our study has numerous strengths. The model accounted for all costs related to administration of the treatments, including administration supplies and IV preparation, premedications/concomitant medications, oncologist office visits, laboratory testing, and administration-related AEs. Although real-world practice patterns for our investigational oral drug combination are not yet known, 2 rounds of thorough expert interviews were conducted with oncologists specializing in the treatment of mBC to understand the potential resource utilization and practice patterns that would be associated with this therapy. Furthermore, in-depth scenario analyses projected to be associated with increased clinical experience of prescribing this new regimen, involving variations in the frequency of oncologist and lab-testing visits, were created; univariate sensitivity analysis was also conducted to test the robustness of the model. In addition to these scenario analyses, an additional comparator—weekly IV paclitaxel (80-100 mg/m2)—was included, as it is a routinely used dose of IV paclitaxel in clinical practice. Findings from all scenario analyses showed cost savings associated with home administration of oral paclitaxel and encequidar.

Since this was an early-stage study aiming to understand costs associated only with administration of oral and IV chemotherapy in different settings, the analysis assumed equal efficacy and safety (other than administration-related AEs) among the therapies, and drug acquisition costs were not included. Differential efficacy and safety profile and inclusion of drug acquisition costs will impact the overall economic value associated with this oral regimen. Once the pricing of oral paclitaxel and encequidar has been set, additional key information for payers will be available from other economic evaluations, including budget impact analysis.

The model was constructed from the perspective of US payers; hence, only payer-related direct costs for each administration setting were included. It will be important to investigate the impact of oral paclitaxel and encequidar from a patient’s perspective. These could include both direct costs, such as out-of-pocket expenses for the chemotherapy and travel for infusions, and indirect costs, such as lost productivity associated with IV chemotherapy.

Our study had several limitations. First, only a 6-month treatment duration was assumed in the analysis given the lack of real-world data on treatment duration of oral therapy. It is possible in the real-world setting that the duration of oral chemotherapy could be longer than that of fixed-duration IV chemotherapies. Second, an assumption of 100% adherence to medication and lab testing was made. While adherence might vary in real-world practices, it was important to make this assumption in the study to understand the complete resource utilization (ie, lab testing, office visits) and costs associated with administration of agents in different settings. Third, cost inputs were derived from multiple sources. However, extensive univariate analyses were done to verify the robustness of the model. Fourth, for the private insurer costs of lab testing, mean commercial reimbursement amounts were used in the analysis. However, there could be a high variability in commercial lab testing costs. Finally, while there may be provider incentives associated with the prescribing of IV therapies, those were not included in the analysis due to high variability.

CONCLUSIONS

This study found that home administration of oral paclitaxel and encequidar was associated with total administration cost of $523 PPPM, a cost 64.4% lower than that of once-every-3-weeks IV paclitaxel (175 mg/m², $1469 PPPM) and 63.8% lower than that of protein-bound paclitaxel (260 mg/m²; $1445 PPPM). The findings indicate that home administration of oral paclitaxel and encequidar may result in potential cost savings for payers.

AUTHOR AFFILIATIONS: EPI-Q, Inc (DS), Oak Brook, IL; Athenex, Inc (JW, ID), Schaumberg, IL; Mirador Global (KMF, CC), Kennett Square, PA.

AUTHOR DISCLOSURES: Dolly Sharma is an employee of EPI-Q Inc, which received payment from Athenex associated with the development and execution of this study. Jeffrey Wojtynek and Igoni Dokubo are employed by and hold stock in Athenex, which funded the study. Kathleen M. Fox and Chelsea Cooper are employees of Mirador Global, which received payment associated with the execution of this study.

FUNDING SOURCE: This study was sponsored by Athenex, Inc.

AUTHOR INFORMATION: Concept and design (DS, JW, KMF, CC, ID); acquisition of data (DS); analysis and interpretation of data (DS, JW, KMF, CC, ID): drafting of manuscript (DS); critical revision of manuscript for important intellectual content (DS, JW, KMF, CC, ID); obtaining funding (JW, KMF, ID); administrative, technical, and logistical support (DS); and supervision (JW, KMF, CC, ID).

CORRESPONDING AUTHOR: Dolly Sharma, PhD (dolly.sharma@epi-q.com).

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