Adding everolimus to letrozole in premenopausal patients with hormone-positive advanced breast cancer

This study evaluated the effects and outcomes of adding everolimus (EVE; Afinitor) plus letrozole (LET; Femara) to hormonal therapy for the treatment of premenopausal women with hormone receptor-positive (HR+), HER2-negative (HER2-) advanced breast cancer (BC). The data showed that the combination of EVE+LET improved survival without cancer worsening and protected the bones of cancer spread in these patients.

BC is classified into different subtypes depending on the presence or absence of certain receptors (proteins found on the surface of the cancer cells). HR+ and HER2- BC tests positive for the estrogen and/or progesterone (female sex hormones) receptors and negative for the HER2 protein. This type of cancer accounts for 70% of all BCs. Patients with this subtype of BC commonly receive hormone therapy which acts by decreasing female hormones.

EVE is an immunosuppressant targeted therapy that reduces cancer cell growth and survival. It has been shown previously that EVE plus LET added to hormonal therapy improved survival without cancer worsening in patients with HR+/HER2- BC. However, longer-term data are missing.  

This study involved 137 premenopausal women with HR+/HER2- advanced BC who were previously treated with tamoxifen (Nolvadex). Patients were undergoing standard hormonal therapy. They were then divided into 2 groups. Group 1 included 92 patients who received EVE plus LET. Group 2 included 45 patients who received LET alone. The average follow-up time was 51.3 months.

The average survival without any progression of cancer was 17.5 months in group 1 compared to 13.8 months in group 2. The overall survival (OS) for group 1 was 48.3 months and for group 2 was 50.8 months. These differences were not significant.

In patients who had cancer spread to the internal organs, the average survival without cancer progression was significantly higher in group 1 (16.4 months) compared to 9.5 months for group 2. In patients with cancer spread to the bones, the average survival without cancer worsening for group 1 was also significantly higher (17.1 months) compared to group 2 (10.9 months).

The 1-year frequency of bone metastases was 6% in group 1 and 23.4% in group 2. Patients in group 1 were 74% less likely to have cancer spread to the bones than patients in group 2. Skeletal-related events like bone fracture and spinal cord compression occurred in 6.5% of the patients in group 1 and 11.1% of the patients in group 2.

This study concluded that adding EVE and LET to hormonal therapy LEUP in tamoxifen-treated premenopausal women significantly improved the outcomes of patients with bone or organ metastases and offered bone-protective effects in patients with HR+/HER2- advanced BC.

This study had a small number of participants. The data on the quality of life of the patients was missing. Novartis, the manufacturer of EVE funded this study.