In contrast, 5 patients with mutant cfDNA had no corresponding mutations in matched tumor tissue. This phenomenon has also been reported and could

be explained by tumor heterogeneity: these biopsied tumor tissue samples may not carry the EGFR mutations detected in blood, because these mutations come from different parts of the tumor [25], [26] and [27]. However, 4 of these 5 patients received EGFR-TKIs and had a comparable PFS with those who exhibited Vincristine price wild type in both blood and tumor tissue, suggesting that these mutations detected in blood could be false positive results. There have been a limited number of studies on the correlation between EGFR mutation status in cfDNA and efficacy of EGFR-TKIs [28], [29], [30], [31] and [32]. Though the researchers tend to agree that EGFR activating mutations in cfDNA may be predictive of better response to EGFR-TKIs, they are still uncertain whether EGFR mutation status in cfDNA can predict survival benefit from EGFR-TKIs. In a subgroup analysis of IPASS, ORR was 75.0% (18/24) and 27.1% (19/70) with gefitinib in patients with or without EGFR mutant cfDNA, respectively.

PFS was significantly longer with Selleckchem H 89 gefitinib than carboplatin/paclitaxel in the cfDNA mutant subgroup (hazard ratio [HR], 0.29; 95% CI, 0.14-0.60; P < 0.001) but not in the cfDNA wild-type subgroup (HR, 0.88; 95% CI, 0.61-1.28; P = 0.50) [22]. Xu et al. reported that an significant correlation between EGFR mutations status in plasma and tumor response to gefitinib was observed using ARMS but not denaturing high-performance liquid chromatography (DHPLC), whereas no association between EGFR mutation status

in plasma and PFS or overall survival (OS) was observed no matter using ARMS or DHPLC [33]. Bai et al. detected EGFR mutations in plasma using DHPLC and found that about 62.2% of patients with EGFR mutations responded to gefitinib, whereas 37.8% of patients with wild-type EGFR also responded. They noted that patients with EGFR mutant cfDNA had a significantly Lonafarnib longer PFS than those with wild-type cfDNA (11.1 months versus 5.9 months, P = 0.044), though no difference in OS was seen [25]. In the current study, patients with EGFR activating mutations in tumor tissue had significantly greater ORR and longer PFS with EGFR-TKIs, which accords with the finding of previous clinical trials [4], [5], [6], [7] and [8]. Patients harboring EGFR activating mutations in cfDNA also had significantly higher ORR, which was consistent to that of patients with mutant tumors. In addition, patients with mutant cfDNA tended to have longer PFS than those with wild-type cfDNA, though the difference was not significant. These data suggest that EGFR activating mutations detected in blood may be predictive of improved tumor response and survival benefit from EGFR-TKIs.