Blood. expression of PD-L1 might only signal better outcome with TKIs. Conclusions High PD-L1 5(6)-TAMRA expression was likely to be associated with the presence of EGFR mutation in advanced lung adenocarcinoma. For EGFR wild-type patients, the PD-L1 over expression can be considered as a poor prognostic indicator of OS. [10-12]. Currently, some studies exhibited that PD-L1 was expressed in 19.63%-65.38% of NSCLC [2, 13-16]. Several studies suggested that PD-L1 expression portended inconsistent survival outcomes . For example, a study showed that tumor with a high level of PD-L1 expression was associated with significantly shorter overall survival (OS) in NSCLC patients , while another report showed positive PD-L1 was significantly associated with better survival outcome . Now, the molecular regulatory mechanism of PD-L1 5(6)-TAMRA isn’t comprehensive enough, though two studies found that mutant EGFR could induce PD-L1 expression and 5(6)-TAMRA = 0.041). However, in subgroup of lung adenocarcinoma, there was a borderline difference between PD-L1 expression level and EGFR mutational status (32/56 (57.1%) for wild type and 64/89 (71.9%) for mutant type, respectively, p=0.067). Open in a separate window Physique 2 (A) Positive programmed cell death-ligand 1 (PD-L1) immunohistochemical staining with a membranous pattern. (B) Unfavorable 5(6)-TAMRA PD-L1 immunohistochemical staining. Original magnification, 20 . Associations between PD-L1 expression and the EGFR-TKIs’ efficacy The association between the efficacy of EGFR-TKIs with PD-L1 expression as well as other clinicpathologic factors in advanced NSCLC patients was summarized in Table ?Table2.2. There was no significant relationship between objective response rate (ORR) and PD-L1 expression, as well as age, gender, histopathological type, stage and TKI line. However, patients with mutant EGFR had better ORR than those with wild-type EGFR (odds ratio (OR), 0.266; 95% confidence interval (95%CI), 0.114 to 0.621; p =0.002) and non-smokers also had higher ORR than smokers did (OR, 4.667; 95% CI, 1.716 to 12.693; p 5(6)-TAMRA = 0.003). These results were in accordance with the results of multivariate analysis. Besides, we examined the association between a variety of factors and disease control rate (DCR). We found that there was no significant difference between DCR and PD-L1 status (OR, 0.783; 95% CI, 0.350 to 1 1.751; p =0.551). Whereas, DCR was significantly higher in women than that in men (OR, 3.478; 95% CI, 1.407 to 8.600; P=0.007), in never-smokers than that in smokers (OR, 3.55; 95% CI, 1.589 to 7.930; P=0.002), and in those with EGFR mutation than that in those EGFR with wild type (OR, 0.092; 95% CI, 0.033 to 0.256; P 0.001) (Table ?(Table2).2). And the multivariate analysis revealed that EGFR mutation positivity was an independent factor (OR, 0.113; 95% CI, 0.038 to 0.342; P=0.007). We further divided patients into two subgroups: (I) EGFR wild type (n=71) and (II) EGFR mutant (n=99). No significant differences in two subgroups were found between Rabbit Polyclonal to RPL40 PD-L1 expression and ORR (OR, 0.854; 95% CI, 0.187 to 3.891; P=0.838 and OR, 1.765; 95% CI, 0.715 to 4.353; P=0.218 for group I and group II, respectively), as well as PD-L1 expression and DCR (OR, 1.169; 95% CI, 0.436 to 3.137; P=0.756 and OR, 0.604; 95% CI, 0.096 to 3.822; P=0.593 for group I and group II, respectively). Table 2 The association between PD-L1 expression and EGFR-TKIS’ efficacy in univariate and multivariate logistic regression analysis# and studies to explore molecular mechanisms of combining EGFR-TKIs and anti-PD-1/PD-L1 antibodies are urgently required. Randomized clinical trials to instruct how best to combine therapeutic agents are also needed. Currently, though gefitinib and erlotinib are regarded as the first line treatment of classical EGFR mutant NSCLC patients, a majority of them eventually develop secondary resistance to gefitinib and erlotinib. Previous treatment options for EGFR-TKIs resistance include CO-1686 , AZD9291  and HM61713  for EGFR.
Previous articleWe demonstrated that LXR activation is linked to chemotherapy level of resistance in vitro and in vivo, also to worse individual survivalNext article Inside a phase 2 multicentre study of 117 individuals (median age 80 years), 6 months of neoadjuvant exemestane produced a clinical response rate of 70% but the best response was seen only in 33% of individuals by 3 months of therapy (Mustacchi em et al /em , 2009)