论文部分内容阅读
Significant progress was made last years in the treatment of advanced NSCLC by giving reversible EGFR TKls (tyrosine kinase inhibitors)such as gefitinib and erlotinib to patients(pts) with EGFR positive mutations on exons 19 and 21.In randomized trials response rate (RR) was frequently over 70%, progression free survival (PFS) 9-10 months and median overall survival (OS) was about 2 years when given in first-line treatment.In second-line and maintenance treatments erlotinib demonstrated efficacy regardless of tumor mutation status.New generation oral, irreversible ErbB receptor family inhibitor Afatinib has a high potency and selectivity for EGFR,, HER2 and HER4.In LUX-LUNG 2 study 120 pts in first or second-line were given Afatinib,90 pts 50 mg and 30 pts 40 mg p.o.daily.Pts with exon 19 or 21 mutations had RR=64%, disease control rate (DCR)=88% and median PFS=15 months.LUX-LUNG 1 tribal was randomized phase 3 trial, 585 pts were randomized 2∶1 to Afatinib 50 mg p.o.daily+BSC vs Placebo+BSC.Pts.had to receive 1-2 chemotherapy regimens and be on EGFR TkIs for at least 3 months without disease progression.Median PFS was 3.3 months on Afatinib vs 1.1 months on Placebo, HR=0.38, p<0.0001.Pts with high likelihood of EGFR mutations had median PFS=4.4 months on Afatinib vs 1.0 month on Placebo.Median OS did not differ significantly because of imbalance of further treatments.Cough, dyspnea and pain improved significantly on Afatinib vs Placebo, so did global QOL and fatigue.Conclusion: We are entering an era of personalized medicine, where each line of treatment will be on the basis of the tumor analysis for development of new mutation.