A study published in JAMA Network Open found that using exemestane as adjuvant endocrine therapy for postmenopausal women with early-stage breast cancer was associated with inferior disease-free survival (DFS) and overall survival (OS) outcomes compared to anastrozole or letrozole. 

Third-generation aromatase inhibitors such as anastrozole, letrozole, and exemestane serve as a standard of care for postmenopausal women with HR-positive early-stage breast cancer. However, the comparative effectiveness of these aromatase inhibitors has not been extensively studied in this patient population. 

Researchers conducted a comparative effectiveness study designed to emulate a target trial population. Using administrative data from the French Early Breast Cancer Cohort, they identified postmenopausal women between the ages of 50-75 years who received adjuvant endocrine therapy between 2010 and 2020. 

The study included data from 148,436 women, with a median age of 64 years. The majority of women received letrozole or anastrozole, with a smaller portion receiving exemestane. 

With a median follow-up of 63 months, the researchers observed that patients treated with exemestane under natural persistence had a lower estimated 8-year DFS and OS compared to those treated with anastrozole or letrozole. 

The researchers further noted that patients who initiated adjuvant treatment with exemestane were more likely than those treated with anastrozole or letrozole to discontinue endocrine therapy within 5 years. They noted, however, that even in patients with perfect persistence, treatment with exemestane was associated with lower DFS and OS than other aromatase inhibitors. 

In a sensitivity analysis, the 8-year OS under perfect persistence was 84.8% among patients treated with exemestane plus chemotherapy, compared with 88.4% for anastrozole plus chemotherapy and 87.6% for letrozole plus chemotherapy.

Patients treated with exemestane had a slightly increased risk of diabetes compared to those treated with anastrozole. However, the risk of bone fractures was similar across all three aromatase inhibitors. 

“In the absence of current guidelines for aromatase inhibitor selection, our results favor anastrozole or letrozole as initial treatment. Furthermore, along with the recent adoption of aromatase inhibitors in combination with CDK4/6 inhibitors or ovarian suppression, the results highlight the need for future studies to inform aromatase inhibitor selection across new treatment regimens and specific subpopulations.”

- Elise Dumas, PhD, Institute of Mathematics, Lausanne, Switzerland, and colleagues

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By Cameron Kelsall

Reference:
https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2843178

Disclosures: One author declared financial ties to drugmakers. See full study for details.