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Anastrozole plus fulvestrant vs. anastrozole alone for hormone receptor-positive advanced breast cancer: a meta-analysis of randomized controlled trials

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Abstract

Background

For patients with hormone receptor (HR)-positive advanced breast cancer, whether the combination of anastrozole and fulvestrant is more effective than anastrozole alone is controversial. Our meta-analysis aimed to compare the efficacy and safety of the two therapies.

Methods

We retrieved relevant studies in Embase, the Cochrane Library, Ovid MEDLINE, PubMed, ScienceDirect, Web of Science, Scopus, and Google Scholar. The primary outcomes were overall survival (OS) and progression-free survival (PFS). The secondary outcomes were the disease control rate (DCR), the objective response rate (ORR), and adverse events (AEs).

Results

Five articles based on 4 randomized controlled trials containing 2146 patients were identified in our meta-analysis. The combination group had better efficacy in the endpoints of OS (hazard ratio [HR] 0.86; 95% confidence interval [CI] 0.74–0.99, p = 0.03) and PFS (HR 0.87; 95% CI 0.77–0.97, p = 0.02). Regarding the ORR, DCR, total AEs and grade 3–5 AEs, we found no difference between the two treatments. The combination group showed a clearly higher rate of treatment discontinuations (95% CI 1.05–3.60, p = 0.03) and AEs leading to death (95% CI 1.12–9.11, p = 0.03). The subgroup analysis of AEs showed an increased incidence of extremity or muscle pain, hematologic effects, gastrointestinal disorders, and hot flashes in the combination group.

Conclusions

For HR-positive advanced breast cancer patients, the combination of anastrozole and fulvestrant appears to be superior to anastrozole alone in extending PFS and OS, despite relatively serious AEs.

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Abbreviations

AI:

Aromatase inhibitor

HR-positive:

Hormone receptor positive

OS:

Overall survival

PFS:

Progression-free survival

OSR:

Overall survival rate

PFSR:

Progression-free survival rate

ORR:

Objective response rate

DCR:

Disease control rate

AEs:

Adverse effects

CI:

Confidence interval

A:

Anastrozole

F:

Fulvestrant

PRISMA:

Preferred reporting items for systematic review and meta-analysis

HR:

Hazard ratios

RR:

Risk ratio

RCT:

Randomized controlled trial

GRADE:

Grading of recommendations assessment, development, and evaluation

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Acknowledgements

The authors thank professor Jichun Liu, MD, PhD (The second affiliated hospital of Nanchang University) for his advice on statistics and professor Xiaoshu Cheng, MD, PhD (The second affiliated hospital of Nanchang University) for his data collection. This study was supported by National Natural Science Foundation of China (NSFC), number of grants (81560345), Natural Science Foundation of Jiangxi Province (Grant No. 20161BAB215237). The funding had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Funding

This study was funded by National Natural Science Foundation of China (NSFC), number of Grants (81560345), Natural Science Foundation of Jiangxi Province (Grant No. 20161BAB215237).

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Authors and Affiliations

  1. Department of Thoracic Surgery, The Second Affiliated Hospital of Nanchang University, 1 Minde Road, Nanchang, 330006, China

    Meng Li, Yiting Xiong, Yiping Wei & Wenxiong Zhang

  2. Jiangxi Medical College, Nanchang University, Nanchang, 330006, China

    Meng Li, Yiting Xiong, Chen Liao & Yunyan He

  3. Department of Breast Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, China

    Chen Liao, Yunyan He & Sijia Duan

  4. Department of Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, China

    Fengming Yi

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Contributions

ML had full access to all of the data in the manuscript and takes responsibility for the integrity of the data and the accuracy of the data analysis. Concept and design: All authors. Acquisition, analysis, or interpretation of data: All authors. Drafting of the manuscript: ML and WZ. Critical revision of the manuscript for important intellectual content: ML, YX, CL, MC and FY. Statistical analysis: ML. Supervision: YW and WZ.

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Correspondence to Wenxiong Zhang.

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Electronic supplementary material

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10549_2020_5551_MOESM1_ESM.tif

Supplementary file1 Figure S1 Risk of bias graph and risk of bias summary judged by the Cochrane reviewer’s handbook. (TIF 2656 kb)

10549_2020_5551_MOESM2_ESM.tif

Supplementary file2 Figure S2 Forest plots of RR of OSR for five years associated with anastrozole plus fulvestrant versus anastrozole alone. (TIF 1351 kb)

10549_2020_5551_MOESM3_ESM.tif

Supplementary file3 Figure S3 Forest plots of RR of PFSR for five years associated with anastrozole plus fulvestrant versus anastrozole alone. (TIF 1710 kb)

10549_2020_5551_MOESM4_ESM.tif

Supplementary file4 Figure S4 Forest plots of RR of ORR (A) and DCR (B) associated with anastrozole plus fulvestrant versus anastrozole alone. (TIF 1476 kb)

Supplementary file5 Figure S5 Meta-based influence analysis for comparisons of total AEs. (TIF 949 kb)

10549_2020_5551_MOESM6_ESM.tif

Supplementary file6 Figure S6 Begg’s and Egger’s tests for comparisons of PFS (A), OS (B) and total AEs (C). (TIF 3731 kb)

Supplementary file7 (DOC 64 kb)

Supplementary file8 (DOCX 17 kb)

Supplementary file9 (DOCX 16 kb)

Supplementary file10 (DOCX 23 kb)

Supplementary file11 (DOCX 15 kb)

Supplementary file12 (DOCX 15 kb)

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Li, M., Xiong, Y., Liao, C. et al. Anastrozole plus fulvestrant vs. anastrozole alone for hormone receptor-positive advanced breast cancer: a meta-analysis of randomized controlled trials. Breast Cancer Res Treat 180, 269–278 (2020). https://doi.org/10.1007/s10549-020-05551-3

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