responded (PR or CR) to prior treatment. Primary analysis revealed median OS times of 10.8 months for afatinib plus BSC and 12.0 months for placebo plus BSC. Despite the lack of OS benefit, afatinib provided significantly better results in the secondary endpoints of PFS time. AZD5438 CDK inhibitor at 8 weeks ,and objective RR than with placebo .Afatinib has also been evaluated as first-line and secondline therapy in patients who have not received a first-generation EGFR TKI. LUX-Lung 2 is a single-arm, multicenter, phase II trial evaluating the efficacy of afatinib in patients with stage IIIB/IV mutant EGFR adenocarcinoma and no prior EGFR-targeted therapy.

               Of 129 patients who received treatment ,54 had L858R EGFR mutations, 52 had exon 19 deletions in EGFR, and 23 had other EGFR mutations . By investigator assessment, the objective RR, DCR, median PFS interval, and median OS time were 60%, 86%, 14 months, and 24 months, respectively,AZD5438 602306-29-6  for all patients .The objective RR, DCR, and median PFS were 59%, 83%, and 16.1 months, respectively, for patients with L858R mutations and 69%, 93%, and 13.7 months, respectively, for patients with exon 19 deletions.

                Additional trials of afatinib in NSCLC are ongoing and summarized in Table 2.Expectations have been high for order AZD5438 irreversible HER family inhibitors in the treatment of NSCLC, and results are awaited from ongoing large randomized clinical trials evaluating these agents in NSCLC, particularly in clinically and/or molecularly selected populations. The optimal role of irreversibleHERinhibitors in the treatment of NSCLC has yet to be determined; however, their potential potency in the first-line setting and ability to bind covalently to block the ATP-binding site of mutant EGFR could potentially improve upon outcomes seen with gefitinib and erlotinib. This may be true particularly for specific activating mutations. In NSCLCs with the most Vargatef common EGFR activators, exon 19 deletions and L858R mutations (85% of known mutations), outcomes are better after reversible TKI treatment for patients with exon 19 mutations than for patients with L858R mutations.