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Erlotinib Gefitinib Afatinib

erlotinib gefitinib afatinib

Description

Gefitinib, erlotinib and afatinib are three widely used epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs)for treating advanced non-small cell lung cancer (NSCLC) with proven efficacy. We undertook a systematic review and metaanalysisto synthesize existing studies with direct comparisons of EGFR TKIs in NSCLC in terms of both efficacy and safety.Eight randomized trials and 82 cohort studies with a total of 17,621 patients were included for analysis. Gefitinib and erlotinibdemonstrated comparable effects on progression-free survival (hazard ratio [HR], 1.00; 95% confidence interval [CI], 0.95to 1.04), overall survival (HR, 0.99; 95% CI, 0.93 to 1.06), overall response rate (risk ratio [RR], 1.05; 95% CI, 1.00 to 1.11),and disease control rate (RR, 0.98; 95% CI, 0.96 to 1.01), which did not vary considerably with EGFR mutation status, ethnicity,line of treatment, and baseline brain metastasis status. Gefitinib was associated with more grade 3/4 liver dysfunction,but tended to cause lower rates of dose reduction, treatment discontinuation, total grade 3/4 adverse events (RR, 0.78; 95%CI 0.65 to 0.94), and a number of specific adverse events such as rash and diarrhea. No solid evidence was found that afatinibhad greater efficacy than gefitinib or erlotinib in first-line treatment of EGFR-mutant NSCLC. However, afatinib was moreeffective than erlotinib as second-line treatment of patients with advanced squamous cell carcinoma. The grade 3/4 adverseevents rate of afatinib was comparable to that of erlotinib but higher than that of gefitinib.

Use

Approximately 10%–15% patients with epidermal growth factor receptor (EGFR) mutations harbor non-classical mutations. However, the effects of EGFR-tyrosine kinases (TKIs), particularly second-generation EGFR-TKI (afatinib) compared to first-generation EGFR-TKIs (gefitinib/erlotinib), in patients with non-classical EGFR mutations remain unknown.

Purpose

To compare the efficacy of afatinib versus erlotinib or gefitinib in EGFR TKIs naïve patients with NSCLC.

Conclusion

The current study indicated that erlotinib, gefitinib, afatinib and icotinib shared equivalent efficacy but presented different efficacy-toxicity pattern for EGFR-mutated patients. Erlotinib and afatinib revealed potentially better efficacy but significant higher toxicities compared with gefitinib and icotinib.

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