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Evidence summaries

Aromatase Inhibitors for Treatment of Advanced Breast Cancer in Postmenopausal Women

Aromatase inhibitors (letrozole, anastrozole, exemestane) are effective and may be more effective for increasing survival compared with other endocrine therapy in postmenopausal women with metastatic breast cancer. Level of evidence: "A"

A Cochrane review [Abstract] 1 included 31 studies with a total of 11403 subjects. A significant overall survival benefit for treatment with an aromatase inhibitor (AI) over other endocrine therapies (tamoxifen, megestrol acetate, medroxyprogesterone acetate, hydrocortisone, and fulvestrant) was seen (HR 0.90, 95% CI 0.84 to 0.97; 13 trials). A subgroup analysis of the 3 commonly prescribed third generation AIs (anastrozole, exemestane, letrozole) also showed a similar overall survival benefit (HR 0.88, 95% CI 0.80 to 0.96; 6 trials). There were very limited data to compare one AI with a different AI, but these suggested an advantage for letrozole over anastrozole. AIs have a different toxicity profile to other endocrine therapies. For those currently prescribed, and for all AIs combined, they had similar levels of hot flushes and arthralgia; increased risks of rash, nausea, diarrhoea and vomiting; but a 71% decreased risk of vaginal bleeding and 47% decrease in thromboembolic events compared with other endocrine therapies.

A network meta-analysis 2 assessed 6 first-line endocrine monotherapies (letrozole, anastrozole, exemestane, tamoxifen, fulvestrant 250mg and 500mg) for hormone receptor-positive, human epidermal growth factor receptor-2-negative (HR+, HER2-) metastatic or locally advanced breast cancer in postmenopausal patients. 27 articles of 8 RCTs involving a total of 3492 patients were included. For objective response rate (ORR), the treatments ranked in descending order of effectiveness were letrozole (most effective), exemestane, anastrozole, fulvestrant 500mg, tamoxifen, fulvestrant 250mg . For time to progression/progression-free survival (TTP/PFS), the order was fulvestrant 500mg (most effective), letrozole, anastrozole, exemestane, tamoxifen, fulvestrant 250mg. For direct comparison of different treatments, the results suggested that letrozole was more efficacious for both ORR and TTP/PFS than tamoxifen. Tamoxifen produced more hot flash events than fulvestrant 250mg.

For postmenopausal women with hormone-receptor-positive breast cancer, adjuvant therapy with an aromatase inhibitor is effective. In a prospective randomized, phase 3 trial 3, women (n=3484) who had received 5 years of adjuvant endocrine therapy received anastrozole for an additional 2 years. Disease progression or death occurred in 335 women in each treatment group in the primary-analysis set at 8 years (hazard ratio, 0.99; 95% CI 0.85 to 1.15; P = 0.90).

References

  • Gibson L, Lawrence D, Dawson C, Bliss J. Aromatase inhibitors for treatment of advanced breast cancer in postmenopausal women. Cochrane Database Syst Rev 2009 Oct 7;(4):CD003370. [PubMed]
  • Zhang J, Huang Y, Wang C et al. Efficacy and safety of endocrine monotherapy as first-line treatment for hormone-sensitive advanced breast cancer: A network meta-analysis. Medicine (Baltimore) 2017;96(33):e7846. [PubMed]
  • Gnant M, Fitzal F, Rinnerthaler G et al. Duration of Adjuvant Aromatase-Inhibitor Therapy in Postmenopausal Breast Cancer. N Engl J Med 2021;385(5):395-405. [PubMed]

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