Abstract PS12-24: From clinical trials to clinical practice: Real-life outcome data of everolimus and exemestane in the treatment of patients with metastatic breast cancer
Authors: Abdel-Razeq Hikmat , Sharaf Baha' , Abdulelah Hazem , Inserat Bayan , Al-Tell Abdallah , Salam Mourad , Bater Rayan 
Published: February 2021

Background: Endocrine therapy is commonly utilized in metastatic breast cancer (mBC) especially so among those with limited visceral metastasis. However, resistance to endocrine therapy is commonly encountered. The addition of the mTOR inhibitor everolimus to exemestane, an aromatase inhibitor (AI), can modulate this resistance. This combination was evaluated in phase-III clinical trials and showed significant improvement in progression-free survival (PFS). However, its occasional serious adverse events, especially pneumonitis, had limited its wider adoption and utilization in clinical practice. In this study, we evaluate the efficacy and the prevalence of serious adverse events encountered in real-life practice outside the stringent setup of clinical trials. Methods: Patients with mBC treated with everolimus plus exemestane and followed at our institution were retrospectively reviewed. Diagnosis of interstitial pneumonitis was based on clinical findings and confirmed by imaging studies. Results: Between January 2017 and October 2019, a total of 91 patients fulfilled the inclusion criteria. Patients’ median age (range) was 45 (23-71) years. All were pathologically confirmed hormone receptor positive (HR+) and Human Epidermal Growth Receptor-2 (HER2) negative. The difference between patients enrolled in this study and the randomized Phase-3 BOLERO-2 trial are details in attached Table.

The majority, 85 (93.4%) had invasive ductal carcinoma (IDC), and 4 (4.4%) had invasive lobular carcinoma. Almost two thirds (n=61, 67.0%) had visceral metastasis involving the liver (n=27, 29.7%) and lung (n=19, 20.9%) with 32 (35.2%) had ≥ 3 metastatic sites. Prior to the designated treatment, patients were subjected to several lines of therapy. Prior treatment with aromatase inhibitors, letrozole or anastrozole, was given to 85 (93.4%) patients while 60 (66.0%) have been treated with tamoxifen. Fulvestrant was given as a third line endocrine therapy in 54 (59.3%) patients. In total, 64 (70.3%) patients had three lines of hormonal therapy prior to everolimus and exemestane. After a median (range) follow up of 13 (1-31) months, 26 (28.6%) had partial response and 32 (35.2%) had stable disease. The median time to disease progression (PFS) was 7.8 months. Seventeen (18.7%) of the patients stopped the treatment due to adverse events mostly due to G3-4 interstitial pneumonitis (n=6, 6.6%), stomatitis (n=6, 6.6%) and one case of membranous nephropathy with nephrotic syndrome. Twenty-eight patients (30.8%) required dose reduction due to elevated liver enzymes (n=12, 13.2%), and stomatitis (n=5, 5.5%). Conclusions: Despite enrolling sicker and heavier-pretreated patients, our real-life outcome data for both efficacy and safety of exemestane and everolimus matches those reported in major clinical trials. Such results should assure clinicians and should lead to wider utilization of this oral, chemotherapy-sparing regimen.

Clinical CharacteristicsOur Cohort (%)Bolero (%)p-valueMedian age4662-Visceral Disease67560.052Metastatic SitesLung21290.118Liver30330.534Bone75760.781≥ 3 Sites35360.974Prior treatment with Letrozole/Anastrozole93100&lt;0.001Prior treatment with Tamoxifen6647&lt;0.001Prior treatment with Fulvestrant5917&lt;0.001Prior treatment with chemotherapy for metastatic disease8426&lt;0.001

Citation Format: Hikmat Abdel-Razeq, Baha' Sharaf, Hazem Abdulelah, Bayan Inserat, Abdallah Al-Tell, Mourad Salam, Rayan Bater. From clinical trials to clinical practice: Real-life outcome data of everolimus and exemestane in the treatment of patients with metastatic breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS12-24.