Cost effectiveness of letrozole versus anastrozole in postmenopausal women with HR+ early-stage breast cancer

Abstract

Background:

The Breast International Group (BIG) 1-98 and Arimidex, Tamoxifen Alone or in Combination (ATAC) trials demonstrated that, in postmenopausal women with hormone receptor positive (HR+) early-stage breast cancer, 5 years of initial adjuvant endocrine therapy with letrozole or anastrozole is superior to tamoxifen. With expected generic availability of anastrozole in July 2010 and letrozole in June 2011, there may be financial pressures prior to letrozole's generic availability to start treatment-naïve patients on anastrozole vs. letrozole or to switch patients already receiving letrozole to anastrozole.

Methods:

A Markov model was used to estimate cost per quality-adjusted life-year (QALY) gained with letrozole vs. anastrozole from the US healthcare system perspective. Cost effectiveness was examined separately in treatment-naïve patients and in patients already receiving letrozole. For the latter, cost effectiveness of continued letrozole vs. therapeutic substitution (TS) to generic anastrozole was evaluated separately in cohorts defined on years of endocrine therapy remaining. TS to generic anastrozole was assumed to result in an additional 5% of patients discontinuing endocrine therapy. Probabilities of distant recurrence and death were taken from reports of BIG 1-98, ATAC, the Early Breast Cancer Trialists’ Collaborative Group meta-analysis of tamoxifen, and other published sources. Carry-over effects of aromatase inhibitors were assumed to be proportional to treatment duration. Costs of aromatase inhibitors were assumed to decline by 75% with generic availability.

Results:

In treatment-naïve patients, total expected lifetime costs are $3916 greater with letrozole vs. anastrozole. However, initiation of treatment with letrozole results in a gain of 0.15 QALYs. Cost per QALY gained with letrozole vs. anastrozole is $25 846. In patients already receiving letrozole, the increase in total expected lifetime costs with continued letrozole vs. TS to anastrozole is between $4200 and $4500 in all cohorts. QALYs gained with letrozole range from 0.21 in those with 4 years of endocrine therapy remaining to 0.13 in those with 1 year of therapy remaining. Cost per QALY gained ranges from $20 276 to $34 356.

Conclusion:

For postmenopausal women with HR+ early-stage breast cancer, letrozole is more likely to be cost effective vs. anastrozole in treatment-naïve patients and in patients already receiving letrozole. Limitations of the study include a lack of direct evidence comparing letrozole and anastrozole and lack of data on rates of discontinuation due to therapeutic substitution with aromatase inhibitors.

Key words:

• Adjuvant therapy
• Anastrozole
• Breast cancer
• Cost effectiveness
• Letrozole
• Postmenopausal
• Therapeutic substitution

Transparency

Declaration of funding

Funding for this research was provided by Novartis Pharmaceuticals Corp.

Declaration of financial/other relationships

A.G. has disclosed that she is an employee of Novartis Pharmaceuticals Corp. M.L. and T.E.D. have disclosed that they are employees of PAI (Policy Analysis Inc.), which has received research support and consulting fees from Novartis. T.E.D. has disclosed that he has received honoraria from Novartis.

Some peer reviewers receive honoraria from CMRO for their review work. The peer reviewers of this paper have disclosed that they have no relevant financial relationships.

Acknowledgments

The authors have disclosed that they had no outside editorial assistance in preparing this manuscript.

An abstract that describes preliminary results of the study is published online at www.asco.org and www.jco.org (Delea TE, Lipsitz M, Zelt S, Guo A. Cost effectiveness of letrozole (LET) vs. anastrozole (ANA) in postmenopausal women (PMW) with hormone receptor-positive (HR+) early-stage breast cancer (EBC) based on indirect comparison of BIG 1-98 and ATAC. J Clin Oncol 2010;28(Suppl; abstr e11013)).

Notes

*Femara is a registered trademark of Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.

†Arimidex is a registered trademark of AstraZeneca Pharmaceuticals LP, Wilmington, DE, USA.