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Cochrane Database of Systematic Reviews

Gefitinib for advanced non‐small cell lung cancer

Overview of attention for article published in Cochrane database of systematic reviews, January 2018
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  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (89th percentile)
  • Above-average Attention Score compared to outputs of the same age and source (57th percentile)

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Title
Gefitinib for advanced non‐small cell lung cancer
Published in
Cochrane database of systematic reviews, January 2018
DOI 10.1002/14651858.cd006847.pub2
Pubmed ID
Authors

Esther HA Sim, Ian A Yang, Richard Wood‐Baker, Rayleen V Bowman, Kwun M Fong

Abstract

The role of gefitinib for the treatment of advanced non-small cell lung cancer (NSCLC) is evolving. We undertook a systematic review to evaluate the available evidence from all randomised trials. To determine the effectiveness and safety of gefitinib as first-line, second-line or maintenance treatment for advanced NSCLC. We performed searches in CENTRAL, MEDLINE and Embase from inception to 17 February 2017. We handsearched relevant conference proceedings, clinical trial registries and references lists of retrieved articles. We included trials assessing gefitinib, alone or in combination with other treatment, compared to placebo or other treatments in the first- or successive-line treatment of patients with NSCLC, excluding compassionate use. We used the standard Cochrane methodology. Two authors independently assessed the search results to select those with sound methodological quality. We carried out all analyses on an intention-to-treat basis. We recorded the following outcome data: overall survival, progression-free survival, toxicity, tumour response and quality of life. We also collected data for the following subgroups: Asian ethnicity and positive epidermal growth factor receptor (EGFR) mutation. We included 35 eligible randomised controlled trials (RCTs), which examined 12,089 patients.General populationGefitinib did not statistically improve overall survival when compared with placebo or chemotherapy in either first- or second-line settings. Second-line gefitinib prolonged time to treatment failure (TTF) (hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.75 to 0.90, P < 0.0001) when compared with placebo. Maintenance gefitinib improved progression-free survival (HR 0.70, 95% CI 0.53 to 0.91, P = 0.007) after first-line therapy.Studies in patients of Asian ethnicity or that conducted subgroup analysesSecond-line gefitinib prolonged overall survival over placebo (HR 0.66, 95% CI 0.48 to 0.91, P = 0.01). In the first-line setting, progression-free survival was improved with gefitinib over chemotherapy alone (HR 0.65, 95% CI 0.43 to 0.98, P = 0.04, moderate quality of evidence). Gefitinib given in combination with a chemotherapy regimen improved progression-free survival versus either gefitinib alone or chemotherapy alone (HR 0.69, 95% CI 0.49 to 0.96, P = 0.03; HR 0.69, 95% CI 0.62 to 0.77, P < 0.00001, respectively). In the second-line setting, progression-free survival was superior in patients given gefitinib over placebo or chemotherapy (HR 0.69, 95% CI 0.52 to 0.91, P = 0.009; HR 0.71, 95% CI 0.57 to 0.88, P = 0.002; moderate quality of evidence, respectively). Combining gefitinib with chemotherapy in the second-line setting was superior to gefitinib alone (HR 0.65, 95% CI 0.43 to 0.97, P = 0.04). As maintenance therapy, gefitinib improved progression-free survival when compared with placebo (HR 0.42, 95% CI 0.33 to 0.54, P < 0.00001).Patients with EGFR mutation-positive tumoursStudies in patients with EGFR mutation-positive tumours showed an improvement in progression-free survival in favour of gefitinib over first-line and second-line chemotherapy (HR 0.47, 95% CI 0.36 to 0.61, P < 0.00001; HR 0.24, 95% CI 0.12 to 0.47, P < 0.0001, respectively). Gefitinib as maintenance therapy following chemotherapy improved overall and progression-free survival (HR 0.39, 95% CI 0.15 to 0.98, P = 0.05; HR 0.17, 95% CI 0.07 to 0.41, P < 0.0001, respectively) in one phase III study when compared to placebo.Toxicities from gefitinib included skin rash, diarrhoea and liver transaminase derangements. Toxicities from chemotherapy included anaemia, neutropenia and neurotoxicity.In terms of quality of life, gefitinib improved Functional Assessment of Cancer Therapy-Lung (FACT-L) (standardised mean difference (SMD) 10.50, 95% CI 9.55 to 11.45, P < 0.000001), lung cancer subscale (SMD 3.63, 95% CI 3.08 to 4.19, P < 0.00001) and Trial Outcome Index (SMD 9.87, 95% CI 1.26 to 18.48, P < 0.00001) scores when compared with chemotherapy. This systematic review shows that gefitinib, when compared with standard first- or second-line chemotherapy or maintenance therapy, probably has a beneficial effect on progression-free survival and quality of life in selected patient populations, particularly those with tumours bearing sensitising EGFR mutations.Patients with EGFR mutations lived longer when given maintenance gefitinib than those given placebo.One study conducted subgroup analysis and showed that gefitinib improved overall survival over placebo in the second-line setting in patients of Asian ethnicity. All other studies did not detect any benefit on overall survival. The data analysed in this review were very heterogenous. We were limited in the amount of data that could be pooled, largely due to variations in study design. The risk of bias in most studies was moderate, with some studies not adequately addressing potential selection, attrition and reporting bias. This heterogeneity may have an impact on the applicability of the resultsCombining gefitinib with chemotherapy appears to be superior in improving progression-free survival to either gefitinib or chemotherapy alone, however further data and phase III studies in these settings are required.Gefitinib has a favourable toxicity profile when compared with current chemotherapy regimens. Although there is no improvement in overall survival, gefitinib compares favourably with cytotoxic chemotherapy in patients with EGFR mutations with a prolongation of progression-free survival and a lesser side effect profile.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 300 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 300 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 44 15%
Researcher 34 11%
Student > Bachelor 33 11%
Student > Ph. D. Student 31 10%
Other 13 4%
Other 37 12%
Unknown 108 36%
Readers by discipline Count As %
Medicine and Dentistry 71 24%
Nursing and Health Professions 29 10%
Pharmacology, Toxicology and Pharmaceutical Science 23 8%
Biochemistry, Genetics and Molecular Biology 14 5%
Social Sciences 6 2%
Other 38 13%
Unknown 119 40%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 18. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 15 August 2023.
All research outputs
#2,163,226
of 26,673,263 outputs
Outputs from Cochrane database of systematic reviews
#4,342
of 13,269 outputs
Outputs of similar age
#46,912
of 458,325 outputs
Outputs of similar age from Cochrane database of systematic reviews
#95
of 222 outputs
Altmetric has tracked 26,673,263 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 91st percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 13,269 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 35.8. This one has gotten more attention than average, scoring higher than 67% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 458,325 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 89% of its contemporaries.
We're also able to compare this research output to 222 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 57% of its contemporaries.