Dataset Information

Efficacy and safety of low-dose everolimus combined with endocrine drugs for patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer.

ABSTRACT:

Background

To analyze the efficacy and safety of everolimus 5 mg/day in combination with endocrine drugs in the treatment of hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer using real-world clinical data.

Methods

Clinical data of hormone receptor (HR)-positive and HER2-negative patients with advanced breast cancer treated with everolimus combined with endocrine drugs in our center between August 2012 and May 2017 were retrospectively analyzed. Curative effect and adverse reactions were evaluated.

Results

A total of 110 patients were enrolled in this study, and 87.3% received salvage chemotherapy. The median number of salvage treatment lines was 5 (range: 1-19). The median follow-up duration was 12 months (range: 1-56.3 months), the overall response rate (ORR) was 6.4%, 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). The mPFS for patients who received ≤2 treatment line was 11.8 months (95% CI: 4.3-19.3 months). Univariate and multivariate analyses suggested that absence of liver metastases, secondary endocrine resistance, and number of metastasis sites <3 were the main factors influencing the benefit of everolimus combined with endocrine therapy. The most common adverse events of grade 3 were: stomatitis (5.5%), non-infectious pneumonia (1.8%), and erythra (1.8%). No grade 4 adverse reactions were observed.

Conclusions

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.

SUBMITTER: Zhang HQ

PROVIDER: S-EPMC8573446 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Publications

Efficacy and safety of low-dose everolimus combined with endocrine drugs for patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer.

Zhang Hui-Qiang HQ Zhou Jin-Mei JM Zhang Shao-Hua SH Bian Li L Xiao Jin-Yi JY Hao Xiao-Peng XP Jiang Ze-Fei ZF Wang Tao T

Annals of translational medicine 20211001 19

<h4>Background</h4>To analyze the efficacy and safety of everolimus 5 mg/day in combination with endocrine drugs in the treatment of hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer using real-world clinical data.<h4>Methods</h4>Clinical data of hormone receptor (HR)-positive and HER2-negative patients with advanced breast cancer treated with everolimus combined with endocrine drugs in our center between August 2012 and May 2017 were re ...[more]

PMID: 34805355

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Project description:There is growing interest in the endocrine treatment (ET) of premenopausal women with hormone receptor positive (HR+) metastatic breast cancer (MBC). This review summarizes available data on endocrine therapy for this patient subset and aims to define the most appropriate treatment approach. The combination of luteinizing hormone-releasing hormone (LHRH) agonists plus tamoxifen seems effective and safe and is considered as being superior to either approach alone; still, single-agent therapy remains an acceptable treatment option. Due to their mechanism of action, aromatase inhibitors alone are not suitable for the treatment of premenopausal patients, but the combination with LHRH agonists may result in excellent disease control. Fulvestrant, in conjunction with LHRH agonists, also yields interesting results regarding clinical benefit rate and time to progression; currently, other orally available selective estrogen receptor downregulators are under clinical evaluation. Recently, targeted drugs have been added to ET in order to reverse endocrine resistance, but only limited information regarding their activity in premenopausal patients is available. The cyclin dependent kinase 4 and 6 inhibitor palbociclib when combined with fulvestrant and LHRH agonists was shown to prolong progression-free survival over endocrine therapy alone in pretreated patients; similar results were obtained with the addition of abemacicilib or ribociclib to endocrine therapy. Currently, activity of the mammalian target of rapamycin inhibitor everolimus in combination with letrozole and goserelin is under assessment in premenopausal patients after progression on tamoxifen (MIRACLE trial). IMPLICATIONS FOR PRACTICE:This review provides clinicians with an overview on the available data regarding endocrine treatment of hormone receptor positive (HR+) metastatic breast cancer (MBC) in premenopausal women and summarizes the treatment options available in routine clinical practice. Knowledge of an up-to-date therapeutic approach in women with premenopausal HR+ MBC will lead to better disease management, thereby improving disease control and quality of life while minimizing side effects.

Project description:We aimed to explore what kind of endocrine treatments are optimal for hormone receptor-positive and human epidermal growth factor receptor 2-negative locally advanced or metastatic breast cancer in some specific clinical situations. We searched randomized controlled trials in Embase, Medline, the Cochrane library, and PubMed from inception to April 1, 2020 and performed a network meta-analysis based on a Bayesian fixed-effects model. Progression-free survival (PFS) with hazard ratios and corresponding 95% confidence interval was defined as the primary endpoint, while overall survival (OS), objective response rate (ORR), clinical benefit rate and serious adverse events were used as secondary endpoints. A total of 35 studies involving 12,285 patients and 24 treatment options were included. In general, most co-treatment options prolonged PFS compared to single-agent therapy, of which aromatase inhibitor (AI) plus everolimus and fulvestrant plus palbociclib were probably the most effective agents, and the latter had the best safety record. However, despite the superior efficacy of fulvestrant plus capecitabine for PFS and OS, palpable toxic effects have been demonstrated for this treatment, so its application must be scrupulously considered. The results of subgroup analysis indicated that fulvestrant combined with palbociclib improved prognosis for phosphatidylinositol 3-kinase (PI3K)-mutated patients, PI3K-unmutated patients, patients with endocrine therapy resistance, and visceral metastatic patients, while no obvious improvement was detected in OS. Moreover, the efficacy of fulvestrant plus cyclin-dependent kinase 4/6 (CDK4/6) inhibitors was slightly better than that of AI plus CDK4/6 inhibitors, while AI plus everolimus was more efficacious than fulvestrant combined with everolimus in terms of PFS, OS, and ORR. In conclusion, our results provide moderate evidence that fulvestrant plus palbociclib and AI plus everolimus were the most effective treatments, while the efficacy and safety of fulvestrant plus palbociclib was obviously superior in some specific clinical situations.

Project description:BackgroundResistance to endocrine therapy in breast cancer is associated with activation of the mammalian target of rapamycin (mTOR) intracellular signaling pathway. In early studies, the mTOR inhibitor everolimus added to endocrine therapy showed antitumor activity.MethodsIn this phase 3, randomized trial, we compared everolimus and exemestane versus exemestane and placebo (randomly assigned in a 2:1 ratio) in 724 patients with hormone-receptor-positive advanced breast cancer who had recurrence or progression while receiving previous therapy with a nonsteroidal aromatase inhibitor in the adjuvant setting or to treat advanced disease (or both). The primary end point was progression-free survival. Secondary end points included survival, response rate, and safety. A preplanned interim analysis was performed by an independent data and safety monitoring committee after 359 progression-free survival events were observed.ResultsBaseline characteristics were well balanced between the two study groups. The median age was 62 years, 56% had visceral involvement, and 84% had hormone-sensitive disease. Previous therapy included letrozole or anastrozole (100%), tamoxifen (48%), fulvestrant (16%), and chemotherapy (68%). The most common grade 3 or 4 adverse events were stomatitis (8% in the everolimus-plus-exemestane group vs. 1% in the placebo-plus-exemestane group), anemia (6% vs. <1%), dyspnea (4% vs. 1%), hyperglycemia (4% vs. <1%), fatigue (4% vs. 1%), and pneumonitis (3% vs. 0%). At the interim analysis, median progression-free survival was 6.9 months with everolimus plus exemestane and 2.8 months with placebo plus exemestane, according to assessments by local investigators (hazard ratio for progression or death, 0.43; 95% confidence interval [CI], 0.35 to 0.54; P<0.001). Median progression-free survival was 10.6 months and 4.1 months, respectively, according to central assessment (hazard ratio, 0.36; 95% CI, 0.27 to 0.47; P<0.001).ConclusionsEverolimus combined with an aromatase inhibitor improved progression-free survival in patients with hormone-receptor-positive advanced breast cancer previously treated with nonsteroidal aromatase inhibitors. (Funded by Novartis; BOLERO-2 ClinicalTrials.gov number, NCT00863655.).

Dataset Information

Efficacy and safety of low-dose everolimus combined with endocrine drugs for patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer.

Background

Methods

Results

Conclusions

Publications

Efficacy and safety of low-dose everolimus combined with endocrine drugs for patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer.

Similar Datasets

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