Background: Aromatase inhibitors (AIs) are increasingly used as adjuvant therapy in early-stage breast cancer (EBC) and are associated with accelerated bone-loss. Adjuvant therapy with zoledronic acid (ZOL) has been shown to prevent aromatase inhibitor-associated bone loss (AIBL) in postmenopausal women (PMW) with EBC. This analysis assessed, via a model projecting lifetime incidence of osteoporotic fractures as a function of BMD, the cost-effectiveness of adjuvant ZOL for the prevention of fractures in PMW with hormone receptor positive breast cancer (stage I-IIIa) who receive adjuvant letrozole 2.5 mg daily for 5 years and who had a baseline bone mineral density (BMD) T score of ≥-2. Methods: A Markov model was developed to project the lifetime incidence of osteoporotic fractures, quality-adjusted life years (QALY), and healthcare costs as a function of BMD for women with EBC (aged 60 years) receiving adjuvant AIs (for up to 5 years) alone or with ZOL upfront or delayed. Two strategies of adjuvant ZOL therapy compared to no treatment were modelled: starting ZOL treatment only when BMD levels decreased (“delayed ZOL”) and starting ZOL 4mg i.v. q 6mo simultaneously with AI therapy (“upfront ZOL”). ZOL efficacy was derived from the ZO-FAST study (N=1,060) which reported a 5.41% (p<0.0001) difference in percentage BMD change between both strategies after 3 years. Data for the no-treatment arm came from a separate trial of AI in which patients did not receive ZOL. The model runs in annual cycles, over a lifetime horizon. Future costs and effects were discounted at 3.5% annually. Results: Compared to no treatment, delayed ZOL therapy was associated with an estimated QALY gain of 0.026 (CI95%:0.007 – 0.045) and an additional cost of £ 419 (CI95%: £ 367 – £ 473). Delayed ZOL therapy vs. no treatment was estimated to cost £ 16,069 per QALY. Compared to no treatment, upfront ZOL was associated with a gain of 0.079 QALY (CI95%: 0.059 – 0.100), at an additional cost of £ 1,742 (CI95%: £ 1,676 – £ 1,810). The corresponding cost per QALY gained was therefore estimated at £ 21,973. Compared to delayed ZOL therapy, upfront ZOL resulted in a gain of 0.053 QALY (CI95%: 0.039 – 0.062) and additional costs of £ 1,323 (CI95%: £ 1,280 – £ 1,366). The cost-effectiveness ratio for upfront vs. delayed therapy was therefore £ 24,868 per QALY gained. Conclusions: Based on this analysis, upfront ZOL is shown to result in better health outcomes (QALYs) than either delayed ZOL or no therapy. Both ZOL therapy strategies were shown to result in highly acceptable cost-effectiveness ratios compared to no treatment.

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1111.

2009