Dataset Information

Patients with exon 19 deletion were associated with longer progression-free survival compared to those with L858R mutation after first-line EGFR-TKIs for advanced non-small cell lung cancer: a meta-analysis.

ABSTRACT:

Backgrounds

It has been extensively proved that the efficacy of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) is superior to that of cytotoxic chemotherapy in advanced non-small cell lung cancer (NSCLC) patients harboring sensitive EGFR mutations. However, the question of whether the efficacy of EGFR-TKIs differs between exon 19 deletion and exon 21 L858R mutation has not been yet statistically answered.

Methods

Subgroup data on hazard ratio (HR) for progression-free survival (PFS) of correlative studies were extracted and synthesized based on random-effect model. Comparison of outcomes between specific mutations was estimated through indirect and direct methods, respectively.

Results

A total of 13 studies of advanced NSCLC patients with either 19 or 21 exon alteration receiving first-line EGFR-TKIs were included. Based on the data from six clinical trials for indirect meta-analysis, the pooled HRTKI/chemotherapy for PFS were 0.28 (95% CI 0.20-0.38, P<0.001) in patients with 19 exon deletion and 0.47 (95% CI 0.35-0.64, P<0.001) in those with exon 21 L858R mutation. Indirect comparison revealed that the patients with exon 19 deletion had longer PFS than those with exon 21 L858R mutation (HR19 exon deletion/exon 21 L858R mutation ?=?0.59, 95% CI 0.38-0.92; P?=?0.019). Additionally, direct meta-analysis showed similar result (HR19 exon deletion/exon 21 L858R mutation ?=?0.75, 95% CI 0.65 to 0.85; P<0.001) by incorporating another seven studies.

Conclusions

For advanced NSCLC patients, exon 19 deletion might be associated with longer PFS compared to L858 mutation at exon 21 after first-line EGFR-TKIs.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC4164616 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Publications

Patients with exon 19 deletion were associated with longer progression-free survival compared to those with L858R mutation after first-line EGFR-TKIs for advanced non-small cell lung cancer: a meta-analysis.

Zhang Yaxiong Y Sheng Jin J Kang Shiyang S Fang Wenfeng W Yan Yue Y Hu Zhihuang Z Hong Shaodong S Wu Xuan X Qin Tao T Liang Wenhua W Zhang Li L

PloS one 20140915 9

<h4>Backgrounds</h4>It has been extensively proved that the efficacy of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) is superior to that of cytotoxic chemotherapy in advanced non-small cell lung cancer (NSCLC) patients harboring sensitive EGFR mutations. However, the question of whether the efficacy of EGFR-TKIs differs between exon 19 deletion and exon 21 L858R mutation has not been yet statistically answered.<h4>Methods</h4>Subgroup data on hazard ratio (HR) for prog ...[more]

PMID: 25222496

Similar Datasets

Project description:The impact of combining epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and chemotherapy as first-line therapy for patients with advanced non-small-cell lung cancer (NSCLC) remains controversial. Therefore, randomized trials that compared this combined regimen with chemotherapy or EGFR-TKIs monotherapy were included for this meta-analysis. We used published hazard ratios (HRs), if available, or derived treatment estimates from other survival data. Pooled estimates of treatment efficacy of the combined regimen in the entire unselected population and selected patients by EGFR-mutation status and smoking history were calculated. Eight trials eventually entered into this meta-analysis, including 4585 patients. Overall, the combined regimen significantly delayed disease progression (HR?=?0.81, 95% CI 0.69-0.95, P?=?0.01); subgroup analysis showed significantly higher progression free survival advantages in Asian patients (P<0.001), with sequential combination of TKIs and chemotherapy (P?=?0.02). In selected patients by EGFR-mutation, both mutation positive (HR?=?0.48, 95% CI 0.28-0.83, P?=?0.009) and negative (HR?=?0.84, 95% CI 0.72-0.98, P?=?0.02) patients gained progression free survival benefit from the combined regimen, albeit the magnitude of benefit was marginally larger in mutation positive patients (P?=?0.05). In selected patients by smoking history, never/light smokers achieved a great progression free survival benefit from the combined regimen (HR?=?0.51, 95% CI 0.35-0.74, P?=?0.0004). Unfortunately, the combined regimen had no significant impact on overall survival, irrespective of ethnicity, dose schedules or EGFR-mutation status. Severe anorexia (RR?=?2.01, 95% CI 1.11-3.63; P?=?0.02) and diarrhea (RR?=?2.70, 95% CI 1.94-3.76; P<0.001) were more frequent in the combined regimen arm. This strategy of combining EGFR-TKIs and chemotherapy deserved to be considered in the future, although it is not approved for advanced NSCLC at the moment.

Dataset Information

Patients with exon 19 deletion were associated with longer progression-free survival compared to those with L858R mutation after first-line EGFR-TKIs for advanced non-small cell lung cancer: a meta-analysis.

Backgrounds

Methods

Results

Conclusions

Publications

Patients with exon 19 deletion were associated with longer progression-free survival compared to those with L858R mutation after first-line EGFR-TKIs for advanced non-small cell lung cancer: a meta-analysis.

Similar Datasets

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