Afinitor is indicated for the treatment of hormone-receptor-positive, HER2/neu-negative advanced breast cancer, in combination with exemestane...

AFINITOR is a kinase inhibitor indicated for the treatment of:...Postmenopausal women with advanced hormone receptor-positive, HER2­ negative breast cancer in combination with exemestane after failure of treatment with letrozole or anastrozole.

HER2 Negative Breast Cancer: Invasive Breast Cancer…SYSTEMIC THERAPY FOR ER - AND/OR PR - POSITIVE RECURRENT OR STAGE IV (M1) DISEASE…HER2-Negative and Postmenopausal or Premenopausal Receiving Ovarian Ablation or Suppression…Preferred Regimens...Everolimus + endocrine therapy (exemestane, fulvestrant, tamoxifen)

A proposed treatment algorithm for the management of hormone receptor (HR)-positive, HER2-negative MBC...Recommendations...Second-line treatment...Everolimus/exemestane is an option since it significantly prolongs PFS...

≥18 years with HR +, HER2 - MBC were classified into the following cohorts (Cs) based on different sequential use of drugs: C1: Hormonal therapy as First line therapy (FLT) followed by CDK 4/6i combinations, Everolimus combinations (EC) and Chemotherapy (CT) C2: CDK 4/6i combinations as FLT followed by EC and CT;...Test of proportions generated statistically significant results between C1&C2 showing that more patients tend to survive longer when they receive CDK4/6i combinations as FLT (C2 80% vs. C1 87%).

...- Metastatic breast cancer HR+ (Hormone Receptor positive), HER2/neu negative (Human Epidermal Growth Factor Receptor-2)...

...- Postmenopausal advanced hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer after failure of treatment with letrozole or anastrozole...

...- Patients must have a histologically confirmed diagnosis of hormone receptor positive, HER2 negative invasive breast carcinoma....

...- Patients currently treated with everolimus for any type of cancer, such as the EMA registered indications i.e. advanced (Hormone-Receptor [HR]-positive, HER2-negative) breast cancer, metastatic renal cell carcinoma (mRCC) or neuroendocrine tumour (NET) of pancreatic, gastrointestinal or lung origin....

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Thirteen patients who received everolimus as a post-treatment after CDK4/6 inhibitor therapy from December 2017 to July 2021 were retrospectively reviewed….The overall response rate and clinical benefit rate were 15.3% (2/13) and 46.2% (6/13), respectively....Considering there is a mechanism of resistance to CDK4/6 inhibitors, everolimus would be important as an effective post-treatment for HR+ or HER2-negative metastatic and recurrent breast cancers treated with CDK4/6 inhibitors in clinical settings.

Overall, 204 HR+, HER2- MBC patients treated with EVE + EXE after progressing following prior endocrine treatment were included....The objective response rate, median PFS, and median OS were 33.4%, 8.9 months, and 23.4 months, respectively....Multivariate analysis revealed that negative progesterone receptor status was a significant determinant of poor treatment response (p = 0.035) and PFS (p = 0.024)....We confirmed the favorable efficacy and safety profile of EVE + EXE for HR+, HER - MBC patients.

The objective response rate, median PFS, and median OS were 33.4%, 8.9 months, and 23.4 months, respectively….We confirmed the favorable efficacy and safety profile of EVE + EXE for HR+, HER2- MBC patients.

Clinical data of hormone receptor (HR)-positive and HER2-negative patients with advanced breast cancer treated with everolimus combined with endocrine drugs...were retrospectively analyzed....the clinical benefit rate (CBR) was 31.8%, the median progression-free survival (mPFS) was 4.0 months (95% CI: 2.9-5.1 months), and the median overall survival (OS) was 17 months (95% CI: 12.1-21.9 months)....Our results showed that everolimus (5 mg/day) combined with endocrine therapy was effective and relatively safe for patients with hormone receptor-positive, HER2-negative metastatic breast cancer.

DESIREE met its primary objective and showed that a dose escalation schema of everolimus over three weeks can be successfully used in pts with HR+/HER2- mBC to prevent the onset of mucositis G≥2 without affecting efficacy.

Patients receiving everolimus plus letrozole achieved a significantly longer median PFS compared with those receiving letrozole alone (19.4 months [95% CI, 16.3-22.0 months] vs 12.9 months [95% CI, 7.6-15.7 months]; hazard ratio, 0.64 [95% CI, 0.46-0.89]; P = .008)...PFS was significantly longer among premenopausal patients with HR-positive/ERBB2-negative advanced breast cancer who received everolimus plus letrozole than among those who received letrozole alone.

Everolimus combined with fulvestrant is not superior to everolimus combined with AI in HR-positive, HER2-negative breast cancer patients. For postmenopausal patients, patients without bone metastasis, and patients with visceral disease, everolimus combined with AI is a better choice.

We retrospectively evaluated patients with HR+, HER2 negative ABC treated with everolimus/exemestane...Overall response rate was 14.3% (1 complete response and 8 partial responses)...Median PFS was 5.6 months (CI95% 2.4-8.8) and median OS was 25.4 months (CI95% 10.3 40.5)...Our results confirm the effectiveness and safety of everolimus/exemestane in real-world setting and support its use mainly before palliative ChT.

The EVEREXES trial initiated in 2012, provided early access to the first dual blockade treatment with EVE + EXE in patients with HR+, HER2 - ABC in Asia and other emerging growth countries…..Confirmed overall response rate (ORR) was achieved for 19.6% of the patients. Efficacy of EVE + EXE across subgroups (prior CT, line of treatment, and presence of visceral metastases) was maintained.

This study assesses the use and efficacy of everolimus exemestane in patients with metastatic HR+ HER2- breast cancer previously treated with endocrine therapy (ET) or endocrine therapy + CDK4/6i….This study suggests that EE remains an effective treatment option after prior ET or ET + CDK4/6i use. Median TTNT of EE was longer for patients who received prior ET, whereas median OS was longer for patients who received prior ET + CDK4/6i...EE remains an effective treatment option regardless of prior treatment option.

We hypothesized that the additional use of trastuzumab (T) or everolimus (E) could restore sensitivity to ET in patients with endocrine-resistant, HR-positive, HER2-negative MBC. These results suggest that E, but not T, can potentially reverse resistance to ET in patients with endocrine-resistant HR-positive, HER2-negative MBC.

...68 HR+/HER2- MBC patients were included in this exploratory study who received everolimus at the dose of 5mg...PFS for the first and second-line is significantly longer than that for the third-line or later (12.9months vs. 4.6months, P= 0.009, HR = 0.395, 95% CI = 0.192-0.811). 11(16.2%) achieved partial response (PR), 42(61.7%) had stable disease (SD), and 15(22.1%) reported progressive disease (PD). The ORR and CBR were 16.2%, 35.2%, respectively.

Everolimus combined with endocrine therapy has significant clinical efficacy in patients with HR-positive/HER-2-negative advanced breast cancer, and can effectively improve the survival of patients with tolerable adverse reactions.

Furthermore, it showed EVE + AI was superior to EVE + FUL in some subgroups: postmenopausal group (hazard ratio, 0.50; 95% CI, 0.26-0.98); without bone metastasis group (hazard ratio, 0.22; 95% CI, 0.06-0.80); visceral disease group (hazard ratio, 0.37; 95% CI, 0.20-0.69). EVE combined with endocrine therapy is an effective treatment option for Chinese patients with hormone-receptor-positive (HR+), human epidermal growth factor receptor-2-negative (HER2-) breast cancer, although EVE + FUL was not superior to EVE + AI.

...patient affected by HR+ HER2- MBC...A third line treatment with Eve (10 mg once daily) plus Exe (25 mg once daily) was initiated. The disease started to respond after 4 months of treatment and the best response was obtained after 39 months of treatment reaching complete response of the liver disease...