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

Survival benefits from lapatinib therapy in women with HER2-overexpressing breast cancer: a systematic review

AY Yip, LA Tse, EY Ong, and LW Chow.

Review published: 2010.

Link to full article: [Journal publisher]

CRD summary

The review concluded that addition of lapatinib to conventional treatment might offer superior survival benefit to patients with advanced metastatic human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer. The review was somewhat limited by its searches and reporting, but the authors' suitably cautious conclusion appears likely to be reliable.

Authors' objectives

To assess the survival benefits of lapatinib for patients with human epidermal growth factor receptor 2 (HER2)-overexpressing advanced or metastatic breast cancer.

Searching

MEDLINE, EMBASE and the Cochrane Breast Cancer Group Trials Register were searched between 2000 and 2008 for studies in English. Search terms were reported. Abstracts from the American Society of Clinical Oncology meetings and San Antonio Breast Cancer Symposia proceedings were also searched. Experts were contacted, and trial protocols searched, to help to identify further studies. Only studies published as peer-reviewed articles or publicy available abstracts were included.

Study selection

Randomised controlled trials of lapatinib (alone, in combination with, or following other therapies) in women with breast cancer were eligible for inclusion. Trials that compared different doses of lapatinib were excluded.

The outcomes of interest were overall survival, progression-free survival, mortality, time to disease progression, objective response rate, clinical benefit rate, and toxicity.

The included trials were all of lapatinib taken with another treatment (capecitabine, paclitaxel, or letrozole) compared with the other treatment alone or the other treatment plus placebo. Included eligible patients had locally advanced or metastatic HER2-positive breast cancer. Two trials were of first-line treatment, and one trial was of patients who had progressed after treatment with anthracycline, taxane, and trastuzumab.

Two reviewers independently selected studies, with disagreements resolved by consensus, or by a third reviewer.

Assessment of study quality

The authors stated that two reviewers independently assessed study quality according to the following criteria: randomisation sequence generation; allocation concealment; blinding of participants, personnel, and outcome assessors; incomplete outcome data; selective outcome reporting, and other potential threats to validity. Details on power calculations for sample size, and use of intention-to-treat analysis were tabulated.

Data extraction

Data were extracted for patients with HER-2 positive breast cancer in order to calculate hazard ratios (HR) or odds ratios (OR) with 95% confidence intervals (CI).

The authors did not state how many reviewers extracted data.

Methods of synthesis

Meta-analyses of pooled hazard ratios or odds ratios were performed using a random-effects model. Heterogeneity was assessed using the χ2 test and I2 statistic.

Results of the review

Three RCTs were included in the review (n=704 patients). The authors reported that all trials were good and of high quality, but the only details reported were that all trials used sample size calculations and intention-to-treat analysis.

Treatment with lapatinib favoured significantly better outcomes in terms of progression-free survival (HR 0.61, 95% CI 0.50 to 0.74; three RCTs), overall survival (HR 0.76, 95% CI 0.60 to 0.97; three RCTs), objective response rate (OR 2.15, 95% CI 1.48 to 3.11; three RCTs) and clinical benefit rate (OR 2.23, 95% CI 1.59 to 3.12; three RCTs). There was no evidence of statistical heterogeneity.

No safety data were reported.

Authors' conclusions

The addition of lapatinib to conventional anticancer treatment might offer superior survival benefit to patients with advanced metastatic human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer.

CRD commentary

The review addressed a clear question, supported by appropriate eligibility criteria. Three databases were searched and searches were also made for unpublished studies, although the restriction to articles written in English meant some relevant studies may have been missed. Independent duplicate study selection and quality assessments reduced the risk of reviewer error and bias affecting the review (although details were not given for the data extraction process).

Trial quality was assessed and was used in interpreting the review results, although the specific details for individual trials were not presented, which made it more difficult to assess their reliability. Also, very few participant characteristics or intervention dose/duration data were presented. Suitable methods were used to pool data and assess heterogeneity.

The review was somewhat limited by its searches and reporting, but the authors' suitably cautious conclusions appear likely to be reliable.

Implications of the review for practice and research

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

Research: The authors cited two large ongoing trials comparing lapatinib with trastuzumab.They also stated a need for further investigations on use of lapatinib in combination with anticancer agents.

Funding

No external funding.

Bibliographic details

Yip AY, Tse LA, Ong EY, Chow LW. Survival benefits from lapatinib therapy in women with HER2-overexpressing breast cancer: a systematic review. Anti-Cancer Drugs 2010; 21(5): 487-493. [PubMed: 20220514]

Indexing Status

Subject indexing assigned by NLM

MeSH

Antineoplastic Agents /therapeutic use; Breast Neoplasms /drug therapy /metabolism /mortality; Female; Humans; Quinazolines /therapeutic use; Receptor, ErbB-2 /metabolism; Survival Analysis

AccessionNumber

12010003675

Database entry date

08/12/2010

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: 20220514