The Effect of Next-Generation TKI in Non-Small Cell Lung Cancer after Failure of First-Line Treatment: a Meta-Analysis

Resistance develops against first-generation tyrosine kinase inhibitors (TKIs), which target the epidermal growth factor receptor (EGFR), after a while for non-small-cell lung cancer (NSCLC). Recently, researchers have developed specific inhibitors against them. Among those inhibitors, next-generation EGFR-TKIs have gained prominence due to the greater efficacy and more favorable tolerability. Today, the efficacy of next-generation EGFR-TKIs in patients with advanced NSCLC after failure on first-generation EGFR-TKIs still remains under investigation. The aim of this meta-analysis was to systematically assess the efficacy and safety profiles of next-generation EGFR-TKIs in advanced NSCLC after failure on first-generation EGFR-TKIs. We performed a comprehensive search of the several electronic databases to September, 2018 to identify clinical trials. The primary endpoint was overall survival (OS), progression-free survival (PFS), disease controlled rate (DCR), objective response rate (ORR), and adverse events (AEs). Severe adverse events (AEs) (grade ≥ 3) based on the EGFR-TKIs were analysed. Odds Ratio (OR) along with 95% confidence interval (95% CI) were utilized for the main outcome analysis. In total, we had 3 randomized controlled trials in this analysis. The group of next-generation EGFR-TKIs was significantly improved PFS (OR = 0.34,95%CI = 0.29–0.40, P < 0.00001), as well with the ORR (OR = 10.48,95%CI = 3.87–28.34, P < 0.00001) and DCR (OR = 6.03,95%CI = 4.41–8.25, P < 0.00001), respectively. However, there is no significant difference in overall survival with next-generation EGFR-TKIs (OR = 1.05,95%CI = 0.85–1.31, P = 0.66). While, the OR for the treatment-related AEs of grade 3 or 4 (diarrhoea, rash/acne, nausea, vomiting, anemia) between the patients who received next-generation EGFR-TKIs and chemotherapy did not show safety benefit (P>0.05). Next-generation EGFR-TKIs was shown to be the better agent to achieve higher response rate and the longer PFS in NSCLC patients as the later-line therapy for previously treated patients with first-generation EGFR-TKIs. While, the benefit of the OS and safety compared with the chemotherapy did not achieved. Further research is needed to develop a database of all EGFR mutations and their individual impact on the differing treatments.