Abstract

Abstract Objective: Elderly patients with low-risk hormone-positive breast cancer are at risk of over treatment. Avoidance of radiation therapy (RT) in favor of endocrine therapy alone was first heralded as the optimal conservative strategy due to logistical simplicity, low acute sequelae and a reduction of contralateral cancers not seen with RT. However, long-term use of aromatase inhibitors (AI) is not without costs and morbidity, often leading to low compliance and notable late effects. We therefore performed a cost-effectiveness analysis to compare the outcomes and costs between AI for five years without RT versus hypofractionated RT alone without endocrine therapy. Materials and Methods: Using data from available phase III trials and meta-analyses, we constructed a patient-level microsimulation Markov decision model to replicate the comparative outcomes between the strategies above from the societal perspective among 200,000 simulated patients. Five years of anastrozole was compared to a 15-fraction hypofractionated whole breast RT course without boost in a cohort of patients with low-risk disease as defined by CALGB 9343 entry criteria. Noncompliance with AI was modeled from recent population-based data. Relative effectiveness on ipsilateral breast tumor recurrence and contralateral breast cancers were based off the NSABP B-21 trial, adjusted to match the modern outcomes demonstrated in CALGB 9343 and PRIME II with further adjustment for AI over tamoxifen (ATAC, EBCTCG meta-analysis). Indirect costs of travel were accounted for, as were the costs of common and serious side-effects from RT (dermatitis, fibrosis, second malignancy, heart disease) and AI (arthralgia, hot flashes, osteopenia, fracture, thrombosis). A 1-year cycle time and lifetime horizon were used, with all costs adjusted to 2018 US dollars and extracted primarily from Medicare reimbursement data. The primary measure of efficacy was the quality-adjusted life-year (QALY) with age-adjusted utilities extracted from the literature. Half-cycle correction and a 3% discount rate were applied. Probabilistic sensitivity analysis was used to vary all parameters simultaneously. Results: On average, RT was approximately $3,981 more expensive than endocrine therapy over the lifetime horizon. Under a number of assumptions, RT appeared similar in long-term effectiveness to AI therapy, with a difference of less than 0.03 quality-adjusted life years. Given the low value of the denominator in the incremental cost-effectiveness ratio (ICER), RT did not meet the formally defined $100,000/QALY threshold. On one-way sensitivity analysis, the ICER was particularly sensitive to the incidence and impact of salvage strategies for recurrence, treatment of contralateral breast cancers, cardiac events and fracture rates. Conclusions: Modeling with the available evidence suggests it is likely that quality-of-life after RT-alone is nearly identical to an AI-alone strategy but associated with a small increase in cost. These results suggest select patients at risk of noncompliance can safely be treated with RT-alone rather than AI alone. Given the relative pros and cons of each strategy, RT-alone should be considered for select elderly low-risk breast patients. Citation Format: Ward MC, Vicini F, Chadha M, Pierce L, Recht A, Hayman J, Thaker N, Khan A, Keisch M, Shah C. Evaluating the cost of endocrine therapy vs. radiation therapy alone for low risk hormone positive early stage breast cancer in elderly patients [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-15-02.

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