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Breast cancer

Exemestane in tamoxifen resistance and head-to-head with letrozole

Supported by Pierre Fabre Medicament
Last updated:6th Jun 2024
Published:30th May 2024

Exemestane and OFS show superior outcomes in ILC

By Elizabeth Donald

Professor Michael Gnant considers what the latest data from the SOFT and TEXT trials mean for the treatment of premenopausal women with hormone receptor-positive invasive lobular carcinoma. View transcript

New data from the TEXT and SOFT trials reveal significant treatment benefits for premenopausal women with hormone receptor-positive (ER+) invasive lobular carcinoma (ILC) when treated with exemestane plus ovarian function suppression (E+OFS). These findings, presented by Otto Metzger (Dana-Farber Cancer Institute, Boston, Massachusetts, USA), build on earlier data from the BIG1-98 study, which suggested partial resistance to tamoxifen (T) in postmenopausal women with ILC.

The trials included 4,115 centrally reviewed ER+/HER2-negative tumours, classified as either invasive ductal carcinoma (IDC, n=3,370) or ILC (n=345). The analysis, adjusting for factors including age, tumour size and nodal status, used Cox model analyses to compare the efficacy of E+OFS and T+OFS, with a primary endpoint of breast cancer-free interval (BCFI).

After a median 12 years of follow-up in the SOFT trial, E+OFS showed a significantly greater benefit over T in participants with ILC (HR=0.32; 95% CI, 0.12–0.91) compared with those with IDC (HR=0.71; 95% CI, 0.54–0.93). This interaction was statistically significant (P=0.15). For SOFT+TEXT at 13 years, E+OFS consistently benefited both ILC (HR=0.60; 95% CI, 0.31–1.15) and IDC (HR=0.70; 95% CI, 0.58–0.85).

E+OFS is currently the most effective treatment for ILC, offering significantly improved outcomes over tamoxifen, particularly in luminal A-like and B-like tumour subgroups

Metzger noted that the findings highlight the need for personalised treatment strategies in breast cancer, ensuring patients receive the most effective therapies based on their cancer subtype.

Professor Diana Lüftner explains how the latest analysis of the SOFT and TEXT trials addresses an unanswered clinical question. View transcript

Letrozole vs exemestane: A head-to-head comparison in breast cancer therapy

Jürgen Geisler (Akershus University Hospital, Lorenskog, Norway) and team presented the results of a direct comparison of two pivotal aromatase inhibitors, letrozole and exemestane, focusing on their ability to suppress oestrogen synthesis during neoadjuvant therapy for patients with ER-positive breast cancer.

This crossover study involved 102 patients with postmenopausal breast cancer, who were randomised into two cohorts. Cohort 1 received letrozole (2.5 mg daily) for 3 months, then switched to exemestane (25 mg daily) for the next 3 months. Cohort 2 followed the reverse regimen. Serum levels of estrone, oestradiol, letrozole and exemestane were measured using an ultrasensitive liquid chromatography with tandem mass spectrometry assay, ensuring precise monitoring of drug efficacy.

Results showed that letrozole achieved superior suppression of serum oestrogen levels compared with exemestane. In cohort 1, estrone and oestradiol levels significantly decreased to 0.2 pmol/L and 0.4 pmol/L, respectively, while on letrozole but increased after switching to exemestane. In cohort 2, starting with exemestane, letrozole further reduced oestrogen levels upon crossover. Notably, 94% of patients on letrozole had estrone levels below the quantification limit, compared with only 35% on exemestane. Serum drug levels confirmed adherence and correlated with the degree of oestrogen suppression.

Both drugs significantly reduced Ki-67 levels across all BMI categories. Notably, women with obesity experienced a more substantial reduction in Ki-67 levels (81% with letrozole and 84% with exemestane) compared with their normal BMI counterparts (49% and 63%, respectively). This suggests that higher baseline oestrogen levels in women with obesity might lead to more pronounced decreases during therapy, resulting in greater suppression of Ki-67 levels.

The study conclusively demonstrates letrozole’s superior efficacy in suppressing both serum estrone and oestradiol levels compared with exemestane

Geisler concluded that these findings highlight the potential for personalised treatment plans based on patient BMI, paving the way for more effective breast cancer therapies.


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