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First-line endocrine therapy for postmenopausal patients with hormone receptor-positive, HER2-negative metastatic breast cancer: a systematic review and meta-analysis.

ABSTRACT: BACKGROUND:In establishing the 2018 Breast Cancer Practice Guidelines of the Japan Breast Cancer Society, we explored the optimal first-line endocrine therapy for advanced postmenopausal hormone receptor-positive breast cancer. METHODS:We performed a systematic review of relevant reports from randomized-controlled studies published prior to November 2016 found using medical journal search engines. The main outcomes which we evaluated were progression-free survival (PFS), objective response rate (ORR), disease control rate (CBR), and toxicity. RESULTS:Four controlled trials comparing aromatase inhibitors (AI) and cyclin-dependent kinase (CDK)4/6 inhibitor combination therapy to AI monotherapy, and two controlled trials comparing anastrozole to fulvestrant 500 mg were analyzed. AI/CDK4/6 inhibitor combination therapy significantly improved PFS (Risk Ratio: 0.67, 95%CI 0.60-0.73), increased ORR (Risk Difference: 0.11, 95% CI 0.07-0.16), and increased CBR (Risk Difference: 0.11, 95% CI 0.07-0.15), compared with AI monotherapy. Patients who received this combination therapy had a higher grade???3 adverse event rate more than those who received AI monotherapy (Risk Difference: 43%, 95%CI: 0.39-0.47). Fulvestrant 500 mg alone significantly improved PFS (risk ratio: 0.85, 95%CI 0.72-0.98), but ORR and CBR were similar to those of anastrozole alone. CONCLUSION:In the first-line treatment for advanced postmenopausal hormone receptor-positive breast cancer, a combination therapy of CDK4/6 inhibitors and AI showed significant improvement of PFS, ORR, and CBR but with significant increased toxicities compared with AI alone. Fulvestrant 500 mg monotherapy significantly prolonged PFS compared with AI monotherapy. We must wait for the results of the studies with longer follow-up period.

SUBMITTER: Shimoi T

PROVIDER: S-EPMC7196086 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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First-line endocrine therapy for postmenopausal patients with hormone receptor-positive, HER2-negative metastatic breast cancer: a systematic review and meta-analysis.

Shimoi Tatsunori T Sagara Yasuaki Y Hara Fumikata F Toyama Tatsuya T Iwata Hiroji H

Breast cancer (Tokyo, Japan) 20200211 3

<h4>Background</h4>In establishing the 2018 Breast Cancer Practice Guidelines of the Japan Breast Cancer Society, we explored the optimal first-line endocrine therapy for advanced postmenopausal hormone receptor-positive breast cancer.<h4>Methods</h4>We performed a systematic review of relevant reports from randomized-controlled studies published prior to November 2016 found using medical journal search engines. The main outcomes which we evaluated were progression-free survival (PFS), objective ...[more]

PMID: 32043218

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Project description:BackgroundAlthough endocrine therapy (ET) is the preferred option for hormone receptor-positive HER2-negative metastatic breast cancer (HR+/HER2- MBC), chemotherapy (CT) is still commonly used. The objective of this real-world study was to present the actual choice of first-line treatment for patients with HR+/HER2- MBC and evaluate the consistency with guidelines in China.MethodsPatients with HR+/HER2- MBC between 1996 and September 2018 were identified from of the database of Chinese Society of Clinical Oncology Breast Cancer (CSCO BC). The statistical description was conducted to present the first-line treatment. Factors influencing the prescription of ET or CT were obtained using univariate and multivariate analysis. The consistency of the actual treatment with the guideline of Chinese Society of Clinical Oncology Breast Cancer (CSCO BC guideline) was evaluated.ResultsOf 1,877 patients, 662 (35.3%) received ET, and 1,215 (64.7%) received CT. ET proportion was only 25.4% in 1996-2005 and gradually increased to 44.6% in 2016-2018. Aromatase inhibitors (69% of ET) and taxane-based regimens (66% of CT) were the most commonly used ET and CT, respectively. Univariate and multivariate analysis showed that patients with age ≥60, distant relapse-free interval (DRFI) ≥24 months, ER+/PR+, bone metastasis only, or progression on (neo)adjuvant ET were preferably chosen for ET as first-line treatment. Factors associated with preferring CT were de novo stage IV, liver or lung metastasis. 17.2% of patients (322 cases) who had neither visceral metastasis nor progression on (neo)adjuvant ET wrongly received CT instead of ET, which is inconsistent with CSCO BC guideline. More than half of patients receiving CT discontinued their initial treatment due to adverse events and other non-disease progression reasons.ConclusionsAlthough high proportion of HR+/HER2- MBC patients received CT as first-line treatment in China, it is gratifying to see that the proportion of patients receiving ET has gradually increased. Our study revealed that 17.2% of patients were over-treated according to CSCO BC guideline, which may provide data to promote guideline adherence. The clinical application for ET should be appropriately expanded in first-line treatment, especially for patients without visceral disease and proof of endocrine resistance.

Project description:BACKGROUND:Response rates to single agent immune checkpoint blockade in unselected pretreated HER2-negative metastatic breast cancer (MBC) are low. However, they may be augmented when combined with chemotherapy. METHODS:We conducted a single-arm, phase II study of patients with triple negative (TN) or hormone receptor-positive endocrine-refractory (HR+) MBC who were candidates for capecitabine. Patients were treated with pembrolizumab 200?mg intravenously day 1 and capecitabine 1000?mg/m2 by mouth twice daily on days 1-14 of a 21-day cycle. The primary end point was median progression-free survival (mPFS) compared with historic controls and secondary end points were overall response rate (ORR), safety and tolerability. The study had 80% power to detect a 2-month improvement in mPFS with the addition of pembrolizumab over historic controls treated with capecitabine alone. RESULTS:Thirty patients, 16 TN and 14 HR+ MBC, were enrolled from 2017 to 2018. Patients had a median age of 51 years and received a median of 1 (range 0-6) prior lines of therapy for MBC. Of 29 evaluable patients, the mPFS was 4.0 (95% CI 2.0 to 6.4) months and was not significantly longer than historic controls of 3 months. The median overall survival was 15.4 (95% CI 8.2 to 20.3) months. The ORR was 14% (n=4), stable disease (SD) was 41% (n=12) and clinical benefit rate (CBR=partial response+SD>6 months) was 28% (n=8). The ORR and CBR were not significantly different between disease subtypes (ORR 13% and 14%, CBR 25% and 29% for TN and HR+, respectively). The 1-year PFS rate was 20.7% and three patients have ongoing responses. The most common adverse events were low grade and consistent with those seen in MBC patients receiving capecitabine, including hand-foot syndrome, gastrointestinal symptoms, fatigue and cytopenias. Toxicities at least possibly from pembrolizumab included grade 3 or 4 liver test abnormalities (7%), rash (7%) and diarrhea (3%), as well as grade 5 hepatic failure in a patient with liver metastases. CONCLUSIONS:Compared with historical controls, pembrolizumab with capecitabine did not improve PFS in this biomarker unselected, pretreated cohort. However, some patients had prolonged disease control. TRIAL REGISTRATION NUMBER:NCT03044730.

Project description:BackgroundHormone receptor-positive/human epidermal growth factor receptor 2-negative (HR + /HER2 -) advanced breast cancer is a prevalent subtype among postmenopausal women. Despite the growing number of randomized clinical trials (RCTs) exploring this topic, the efficacy and safety of first-line and second/further-line treatments remain uncertain. Accordingly, our aim was to conduct a comprehensive evaluation of the efficacy and safety of these therapies through network meta-analysis.MethodsRCTs were identified by searching Pubmed, Embase, and major cancer conferences. The efficacy of interventions was assessed using the hazard ratios (HRs) of progression-free survival (PFS) and overall survival (OS), while safety was indicated by the incidence of any grade adverse events (AEs), grade 3-5 AEs, AEs leading to treatment discontinuation, and AEs leading to death. Both time-variant HRs fractional polynomial models and time-invariant HRs Cox-proportional hazards models were considered for handling time-to-event data. Safety indicators were analyzed using Bayesian network meta-analysis. Additionally, subgroup analyses were conducted based on patient characteristics.ResultsA total of 41 RCTs (first-line 17, second/further-lines 27) were included in the analysis. For first-line treatment, the addition of Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors to endocrine therapy significantly improved therapeutic efficacy in terms of both PFS and OS, demonstrating the best performance across all mechanisms. Specifically, the combination of Abemaciclib and Letrozole demonstrated the most favorable performance in terms of PFS, while Ribociclib plus Fulvestrant yielded the best outcomes in OS. Incorporating the immune checkpoint inhibitor Avelumab into the regimen with CDK4/6 inhibitors and selective estrogen receptor degraders significantly enhanced both PFS and OS in second-line or later treatments. Regarding safety, endocrine monotherapy performed well. Regarding safety, endocrine monotherapy performed well. There is mounting evidence suggesting that most CDK4/6 inhibitors may demonstrate poorer performance with respect to hematologic AEs. However, additional evidence is required to further substantiate these findings.ConclusionsCDK4/6 inhibitors, combined with endocrine therapy, are pivotal in first-line treatment due to their superior efficacy and manageable AEs. For second/further-line treatment, adding immune checkpoint inhibitors to CDK4/6 inhibitors plus endocrine therapy may produce promising results. However, to reduce the results' uncertainty, further trials comparing these novel treatments are warranted.Trial registrationRegistration number: PROSPERO (CRD42022377431).

Dataset Information

First-line endocrine therapy for postmenopausal patients with hormone receptor-positive, HER2-negative metastatic breast cancer: a systematic review and meta-analysis.

Publications

First-line endocrine therapy for postmenopausal patients with hormone receptor-positive, HER2-negative metastatic breast cancer: a systematic review and meta-analysis.

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