August 11, 2022

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Letrozole Anastrozole or Exemestane for breast cancer endocrine therapy?

Letrozole Anastrozole or Exemestane for breast cancer endocrine therapy?

Letrozole Anastrozole or Exemestane for breast cancer endocrine therapy? Letrozole, anastrozole, exemestane,  Which is the best for breast cancer endocrine therapy?

01.  Basic information

Aromatase inhibitors (AI) play an important role in the endocrine therapy of estrogen receptor (ER)-positive breast cancer patients.

Aromatase is the product of the CYP-19 gene, a member of the cytochrome P450 superfamily. It can catalyze the conversion of peripheral androgens into estrogen, while AI can inhibit aromatase, reduce plasma estrogen levels, and inhibit the growth of breast tumor cells.

Common aromatase inhibitors are anastrozole (1 mg/d), letrozole (2.5 mg/d), and exemestane (25 mg/d).  Each of the three AIs has its own characteristics. How should clinicians and patients choose?

Letrozole Anastrozole or Exemestane for breast cancer endocrine therapy?

02.  Comparison of clinical efficacy

FATA-GIM3 research

The FATA-GIM3 study compared the difference between the initial use of AI and tamoxifen after switching to AI. It is also the first time that three different AIs have been compared in the same study.

A total of 3697 patients were enrolled in this study, and they were randomly divided into six groups, namely: tamoxifen 2 years followed by anastrozole 3 years group, tamoxifen 2 years followed by exemestane 3 years group, Tamoxifen 2-year sequential letrozole 3-year group, anastrozole 5-year group, exemestane 5-year group, letrozole 5-year group, plan to compare sequential treatment and initial adjuvant treatment, and three Kind of AI DFS.

The results showed that the 5-year DFS of the anastrozole group was 90% (95% CI 87.9-91.7), the exemestane group was 88% (95% CI 85.8-89.9), and the letrozole group was 89% (95% CI 87.3-91.1). The test showed that the three aromatase inhibitors have no significant differences in efficacy. Therefore, when determining the best treatment method, the patient’s preference, tolerability and economic factors should be considered.

Head-to-head test

A head-to-head prospective randomized comparative trial enrolled 128 postmenopausal hormone receptor-positive advanced breast cancer patients and assigned them to exemestane group and anastrozole group, two groups of ORR (both groups 15%) and OS (31 and 33 months respectively) are similar.

Therefore, according to the above two research data, whether it is hormone receptor-positive early breast cancer or advanced breast cancer, the efficacy of the three aromatase inhibitors is similar.

 

03. Comparison of adverse drug reactions

1) In the FATA-GIM3 trial, the incidence of gastrointestinal side effects in the exemestane group was higher than that in the letrozole group, while the incidence of hypercholesterolemia in the anastrozole group and letrozole group was higher than that in the exemestane group. All other side effects of each drug are similar.

2) AI-related musculoskeletal syndromes (a series of symptoms such as joint pain, joint stiffness, and/or bone pain) often occur in patients using AI.

A meta-analysis compared the bone safety of postmenopausal breast cancer patients receiving aromatase inhibitors, exemestane versus anastrozole (OR = 0.59, p = 0.63) and letrozole (OR = 0.54, p = 0.75) It can reduce the occurrence of bone pain; Compared with Anastrozole (OR = 0.84, p = 0.41) and Letrozole (OR = 0.85, p = 0.73), it can also reduce the onset of fractures; Compared with Anastrozole (OR = 0.55, p = 0.73) The comparison also reduces the occurrence of joint stiffness.

The decrease in bone mineral density in the exemestane group was also less than that in the anastrozole group (hip joint reduction 1.08; lumbar spine: 1.34). This analysis showed that exemestane is the aromatase inhibitor most likely to reduce the incidence of bone-related adverse events.

 

 

04.  Recommendations for clinical selection

Whether it is hormone receptor-positive early breast cancer or advanced breast cancer, the three aromatase inhibitors have similar effects. The clinic can choose one of them according to the patient’s tolerance, and if it cannot tolerate it, switch to the other one.

If the patient is taking cytochrome P450 strong inducers or inhibitor drugs, to avoid drug interactions, anastrozole can be the first choice.

Patients with moderate to severe liver damage and severe renal damage should not use anastrozole. Exemestane should be used with caution and letrozole is the choice, but close monitoring is required.

Patients with hypercholesterolemia can choose exemestane as the first choice for steroidal aromatase inhibitor exemestane. Patients with osteoporosis and high risk of fracture can also choose exemestane.

During AI treatment, patients need to be recommended to use bisphosphonates to prevent bone adverse events.

(source:internet, reference only)


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