Short-Term Costs Associated With Primary Prophylactic G-CSF Use During Chemotherapy
Published Online: February 13, 2013
Suja S. Rajan, MHA, MS, PhD; William R. Carpenter, MHA, PhD; Sally C. Stearns, PhD; and Gary H. Lyman, MD, MPH
Chemotherapy is vital for breast cancer treatment because it prevents recurrence and reduces mortality.1-8 Despite the demonstrated efficacy of first-course chemotherapy, compliance with recommended therapy is limited by chemotherapy-induced acute toxicities like neutropenia. Neutropenia is one of the most common reasons for chemotherapy dose reductions, delays, or discontinuation.9-11 Chemotherapy dose reductions make it difficult to prevent tumor regrowth, reduce chemotherapy effectiveness, increase the probability of recurrence and mortality, and might also increase the overall treatment costs.9,10,12-19 The rate of neutropenia is especially high among the elderly (age >65 years).20
The primary prophylactic (PP) use of granulocyte-colony stimulating factor (G-CSF) helps prevent neutropenia and sustain chemotherapy dose intensity.9,16,21-24 Use of PPG-CSF can also reduce costs associated with neutropenia-related hospitalizations and systemic antibiotic administration used to treat neutropenia-associated infections and fever.
More than 60,000 neutropenia hospitalizations occur each year in the United States,25 and each hospitalization could cost $10,000 to $30,000 on average.26-29 Administration of PPG-CSF might offset neutropenia hospitalization costs by reducing both the probability21,24,30-32 and duration21,26,33 of hospitalization. Other factors that might reduce costs for patients receiving PPG-CSF during the first year after diagnosis (when bulk of the cancer therapy is administered) include reducing the need for second-course chemotherapy due to an ineffective first course, a shorter but more intense first course of chemotherapy, and recurrence prevention. Nevertheless, G-CSFs themselves are expensive. Hence, their administration should be justified both clinically and economically.
Evidence supporting the cost-effectiveness of PPG-CSF in cancer patients is ambiguous. Some clinical trials and observational studies have documented cost-savings from PPG-CSF administration due to reduced hospitalization costs or overall treatment costs.34-36 Other studies have demonstrated no change in costs because the cost savings are offset by G-CSF administration costs.26,37,38 Lyman et al determined that PPGCSF is cost-effective only for patients with >20% risk of chemotherapyinduced febrile neutropenia.21
However, studies based on clinical trials underreport the incidence and costs of treatmentrelated adverse events because they exclude high-risk patients like elderly, have short study durations, and have incomplete adverse event documentation.39-41 The American Society of Clinical Oncology guideline for GCSF use identifies the lack of evidence for G-CSF–related costs and calls for studies establishing the economic impact of G-CSF use.42 The guideline also states that current recommendations for G-CSF use are predominantly based on clinical benefits and not economic outcomes.
The lack of external validity and inadequacies of clinical trials in the elderly call for nationally representative population- based studies to establish the economic impact of PPGCSF use in the elderly.39 This study aims to address this gap and analyzes the effects of PPG-CSF administration on the very first neutropenia hospitalization costs (for patients with any neutropenia hospitalization) and overall first-year Medicare costs after chemotherapy initiation (for the entire study sample) in elderly breast cancer patients.
This paper focuses on the effectiveness of primary prophylaxis and not secondary prophylaxis or therapeutic G-CSF administration. This study also examines the effect of duration of PPG-CSF administration on overall first-year Medicare costs in elderly female breast cancer patients receiving chemotherapy. The commercially available PPG-CSF during the study period (predominantly filgrastim) had to be administered daily for up to 14 days until the absolute neutrophil count reached 10,000 cells per microliter.43 Empirical studies show that PPG-CSF is often administered for 4 to 7 days in practice, and inadequate G-CSF administration is a concern since it is associated with reduced drug effectiveness.30,44,45 Since each shot of PPG-CSF costs more than $250, the study explores costs associated with increased duration of PPG-CSF administration. The effect of PPG-CSF duration on neutropenia hospitalization costs were not estimated due to limited sample size.
This study uses the Surveillance, Epidemiology and End Results (SEER) data from 16 registries containing newly diagnosed breast cancer cases from 1994 to 2002 linked to Medicare claims through 2003. The 16 SEER registries are representative of approximately 25% of the US population, of which the Medicare population is a subset.46 The data are valid, high quality, and complete in terms of cancer incidence and diagnosis reporting in the United States.46
The study period begins in 1994 after the introduction of G-CSF Healthcare Common Procedure Coding System codes in Medicare claims. To allow for the assessment of prediagnostic comorbidity from 1 year of Medicare claims prior to diagnosis, the study sample was limited to women aged 66 years and older. Women with stage 0 breast cancer were excluded because they do not require chemotherapy. Women with stage IV disease were excluded because chemotherapy is used as palliative rather than curative therapy in these patients. To ensure complete claims, the sample was limited to women enrolled in both Medicare part A and B, and not enrolled in an HMO, for 1 year before and after their diagnosis. The sample was limited to women whose chemotherapy was initiated within the first 6 months of diagnosis because chemotherapy initiation after 6 months could be for recurrence and not for the primary tumor. The initial study sample thus included 10,441 patients aged 66 years and older who were diagnosed with stage I to III breast cancer during 1994 to 2002 and who received chemotherapy within 6 months of diagnosis. The study period was particularly chosen because the period offers a clean sample for exploring the impact of short-acting PPG-CSF on Medicare costs. The utilization of long-acting pegfilgrastim among Medicare patients began in 2003. Unlike short-acting PPG-CSF, pegfilgrastim is administered once per chemotherapy cycle (every 2-3 weeks); currently both shortand long-acting G-CSFs are used.
Study Measures and Framework
PDF is available on the last page.