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

The role of vandetanib in the second-line treatment for advanced non-small-cell-lung cancer: a meta-analysis of four randomized controlled trials

WX Qi, LN Tang, AN He, Z Shen, and Y Yao.

Review published: 2011.

Link to full article: [Journal publisher]

CRD summary

The review concluded that vandetanib offered clinically and statistically significant improvements in progression-free survival and overall response rates in patients with advanced non-small cell lung cancer but did not benefit overall survival. The small evidence base, differences across trials and borderline significance of progression-free survival results means that some caution is required when interpreting the authors’ conclusions.

Authors' objectives

To assess the efficacy and toxicity of vandetanib in the second-line treatment of advanced non-small cell lung cancer.

Searching

PubMed, EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL) were searched to July 2011 for articles in any language. Search terms were reported. Abstracts presented at the European Society of Medical Oncology (2002 to 2010) and American Society of Medical Oncology (2000 to 2011) were searched.

Study selection

Prospective phase II and III randomised controlled trials (RCTs) of vandetanib versus standard second-line therapy for the treatment of previously treated patients with pathologically confirmed non-small cell lung cancer were eligible for inclusion. Relevant outcomes included overall survival, overall response rate, progression-free survival and adverse events.

The included trials studied vandetanib alone or in combination with docetaxel or pemetrexed versus erlotinib, docetaxel or pemetrexed. Where reported, the median age of patients ranged from 52 to 61 years. Trials were published between 2007 and 2011. Most trials were phase three trials and there was one phase two trial.

The authors did not state how many reviewers undertook study selection.

Assessment of study quality

Quality assessment was undertaken using the Jadad tool of randomisation, blinding and withdrawals and drop-outs, to give a score out of a maximum of five.

The authors did not state how many reviewers undertook quality assessment.

Data extraction

Data were extracted on clinical outcomes and adverse events and used to calculate odds ratios (ORs) or hazard ratios (HRs), with 95% confidence intervals (CIs). Where survival data were not reported, survival curves were deciphered.

Two reviewers independently extracted data.

Methods of synthesis

A fixed-effect meta-analysis was undertaken to calculate pooled odds ratios and hazard ratios, together with 95% CIs. Analyses were undertaken on an intention-to-treat basis. Statistical heterogeneity was assessed using the Χ²and Ι² statistics. A random-effect meta-analysis was used where there was evidence of significant statistical heterogeneity. Publication bias was assessed using funnel plots and Begg’s and Egger’s tests. Subgroup analysis based on study characteristics was undertaken.

Results of the review

Four RCTs were included (3,292 patients, range 127 to 1,391). All of the trials scored the maximum 5 on the Jadad scale, which indicated higher quality.

Compared with control, vandetanib was associated with a borderline statistically significant longer progression-free survival (HR 0.91, 95% CI 0.83 to 1.00; three RCTs; Ι²=42%) and a greater overall response rate (OR 1.49, 95% CI 1.04 to 2.14; four RCTs; Ι²=67%). There was no significant difference in overall survival (three RCTs).

There was no difference in adverse events in grade 3-4 neutropenia, diarrhoea, cough, fatigue, rash or nausea and vomiting. Vandetanib was associated with a statistically significantly lower risk of grade 3-4 anaemia (OR 0.39, 95% CI 0.22 to 0.67; two RCTs; Ι²=45%),

The authors reported that there was no evidence of publication bias.

Authors' conclusions

Therapy with vandetanib offered a clinically meaningful and statistically significant improvement in progression-free survival and overall response rate in patients with advanced non-small cell lung cancer but did not benefit overall survival.

CRD commentary

Inclusion criteria for the review were clearly defined. Several relevant data sources were searched for articles in any language. Publication bias was assessed and was not detected but the meaningfulness of an analysis with fewer than 10 trials was limited. Attempts were made to reduce reviewer error and bias during data extraction; it was not clear whether the same methods were used for study selection and quality assessment. Quality assessment indicated that all of the trials were of higher quality.

The authors noted differences across the trials in terms of drugs, histology, methodologies and criteria that may have influenced results. Data were pooled using appropriate meta-analysis techniques and statistical heterogeneity was reported; there was evidence of statistical heterogeneity for overall response rates. The results for progression-free survival were only borderline significant and may not be reliable. Vandetanib was typically given in combination with other drugs and it was unclear what influence these other treatments had on the results.

The evidence base was small and there were differences across trials. Results for progression-free survival were borderline significant and any clinical significance was unclear. Some caution is required when interpreting the authors’ conclusions.

Implications of the review for practice and research

Practice: The authors stated that therapy with vandetanib regimens might be suggested as second-line treatment for advanced non-small cell lung cancer based on a similar toxicity profile compared with standard second-line therapy.

Research: The authors stated that more trials of second-line vandetanib for advanced non-small cell lung cancer were needed.

Funding

Not stated.

Bibliographic details

Qi WX, Tang LN, He AN, Shen Z, Yao Y. The role of vandetanib in the second-line treatment for advanced non-small-cell-lung cancer: a meta-analysis of four randomized controlled trials. Lung 2011; 189(6): 437-443. [PubMed: 21986852]

Indexing Status

Subject indexing assigned by NLM

MeSH

Adult; Aged; Aged, 80 and over; Antineoplastic Agents /adverse effects /therapeutic use; Carcinoma, Non-Small-Cell Lung /drug therapy /mortality; Humans; Lung Neoplasms /drug therapy /mortality; Middle Aged; Piperidines /adverse effects /therapeutic use; Quinazolines /adverse effects /therapeutic use; Randomized Controlled Trials as Topic; Survival Rate; Treatment Outcome

AccessionNumber

12012000291

Database entry date

06/11/2012

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: 21986852

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