Home > DARE Reviews > Fulvestrant in the treatment of advanced...

PubMed Health. A service of the National Library of Medicine, National Institutes of Health.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet]. York (UK): Centre for Reviews and Dissemination (UK); 1995-.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet].

Fulvestrant in the treatment of advanced breast cancer: a systematic review and meta-analysis of randomized controlled trials

A Valachis, D Mauri, NP Polyzos, D Mavroudis, V Georgoulias, and G Casazza.

Review published: 2010.

Link to full article: [Journal publisher]

CRD summary

This review concluded that fulvestrant had a good tolerability profile and efficacy that was similar to other hormonal agents for treatment of advanced breast cancer. The authors' conclusions reflected the evidence, but they should be viewed with caution given the small number of included trials and the potential for reviewer error and bias.

Authors' objectives

To compare the efficacy and tolerability of fulvestrant versus standard treatments (aromatase inhibitors and tamoxifen) for patients with advanced breast cancer.

Searching

MEDLINE, Web of Science and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for articles in any language up to August 2008. Search terms were reported. Reference lists of relevant trials were handsearched. Further searches involved scanning of symposia proceedings, poster presentations, and abstracts from major cancer meetings (e.g. American Society of Clinical Oncology Annual meetings, San Antonio Breast Cancer Symposium).

Study selection

Randomised controlled trials (RCTs) that compared fulvestrant versus other hormonal therapies in patients with advanced breast cancer were eligible for inclusion. Single arm and dose-escalation trials were excluded.

Primary outcomes were overall survival, time to tumour progression, objective response and clinical benefit. Objective response was defined as the proportion of patients with complete response or partial response after treatment. Clinical benefit was defined as the proportion of patients with an objective response or stable disease lasting at least 24 weeks. Secondary outcomes were the number of adverse events.

Included trials enrolled postmenopausal breast cancer patients whose reported median age was 63 to 67 years. Fulvestrant was administered as a 250mg (intramuscular) preparation once a month in all included trials. Fulvestrant was the first line therapy in one trial and second or greater in the remaining trials. Comparators included anastrozole, exemestane and tamoxifen.

The authors did not state how many reviewers selected studies for inclusion.

Assessment of study quality

Trial quality assessed randomisation, allocation concealment, subject withdrawals and reasons for withdrawals, interim analyses, and intention-to-treat analyses.

The authors did not state how many reviewers assessed trial quality.

Data extraction

Data to enable the calculation of hazard ratios (HRs) for overall survival and time to progression outcomes and odds ratios (ORs) for clinical benefit, objective response and all secondary outcomes, with 95% confidence intervals (CIs), were extracted using 2x2 tables.

The authors did not state how many reviewers extracted data.

Methods of synthesis

Heterogeneity was assessed using X2 statistic. Where there was no evidence of heterogeneity, pooled hazard ratios and 95% confidence intervals were calculated using the Peto method; pooled odds ratios and 95% confidence intervals were calculated using the Mantel-Haenszel method. Where evidence of heterogeneity was found, pooled effect sizes, with 95% confidence intervals, were calculated using the DerSimonian and Laird random-effects method. Standard errors of hazard ratio estimates were indirectly derived from the confidence intervals reported in each trial.

Results of the review

Four RCTs (eight reports) were included in the review (n=2,125 patients, table 1; range 400 to 693). Trial quality was varied: only one trial described the method of randomisation and allocation concealment; three trials were double-blinded; three trials described withdrawals; and none of the trials were stopped early.

No statistically significant differences were found between fulvestrant and other hormonal agents for overall survival, time to progression, clinical benefit, objective response rate or adverse events (three RCTs each).

The incidence of joint disorders was significantly higher in patients receiving hormonal agents other than fulvestrant (pooled OR 0.621, 95% CI 0.424 to 0.909; three RCTs; n=1,544 patients).

Authors' conclusions

Fulvestrant has a good tolerability profile and efficacy that was similar to other hormonal agents for treatment of advanced breast cancer.

CRD commentary

The review addressed a clear question with explicit study selection criteria. Several databases were searched without any restrictions on language or publication date. Efforts were made to search for unpublished studies. Consequently, language and publication biases were unlikely. It was unclear whether review processes were conducted in duplicate, so the possibility of reviewer error and bias could not be excluded.

Trial quality appeared to have been assessed using appropriate criteria. The methods used to combine data and account for statistical heterogeneity were appropriate and justified. The authors appropriately stated that a limitation of the review was the small number of included trials, with differences in design and modes of treatment.

The authors' conclusions reflected the evidence, but they should be viewed with caution given the small number of included trials and potential for reviewer error and bias.

Implications of the review for practice and research

Practice: The authors did not state any implications for practice.

Research: The authors stated that further prospective data are needed to determine the appropriate timing and schedule for administration of fulvestrant.

Funding

Not stated.

Bibliographic details

Valachis A, Mauri D, Polyzos NP, Mavroudis D, Georgoulias V, Casazza G. Fulvestrant in the treatment of advanced breast cancer: a systematic review and meta-analysis of randomized controlled trials. Critical Reviews in Oncology/Hematology 2010; 73(3): 220-227. [PubMed: 19369092]

Indexing Status

Subject indexing assigned by NLM

MeSH

Antineoplastic Agents, Hormonal /therapeutic use; Aromatase Inhibitors /therapeutic use; Breast Neoplasms /drug therapy; Estradiol /analogs & derivatives /therapeutic use; Female; Humans; Randomized Controlled Trials as Topic; Tamoxifen /therapeutic use

AccessionNumber

12010001822

Database entry date

29/06/2011

Record Status

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.

CRD has determined that this article meets the DARE scientific quality criteria for a systematic review.

Copyright © 2014 University of York.

PMID: 19369092

Download

PubMed Health Blog...

read all...

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...