Circulating tumor cells predict prognosis following second-line AZD 9291 treatment in EGFR-T790M mutant non-small cell lung cancer patients

Purpose: AZD9291 has been developed as third-generation epithermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) with activities against T790M mutation. This study aimed to isolate and quantify the circulating tumor cells (CTCs) in non-small cell lung cancer (NSCLC) patients after first-line EGFR TKIs and investigate their role in providing prognostic information. Methods: Enrolled patients confirmed with EGFR T790M mutation received AZD9291 80 mg orally once daily as second-line treatment. Serial blood samples were taken at baseline (CTC-d0) and on day 28 (CTC-d28) following the initiation of AZD9291 for detection of CTCs using the Cell-Search system. Results: The CTC measurements were dichotomized as favorable (<5 CTCs) and unfavorable (>= 5 CTCs) groups. Patients in the favorable group at baseline exhibited significantly longer median progression-free survival (PFS) compared with patients in the unfavorable group (9.3 vs. 6.5 months; p=0.0002). The PFS interval for patients in the favorable group on day 28 was 9.7 months, significantly longer than the median PFS time of 6.2 months achieved by patients in the unfavorable group (p=0.011). In univariate and multivariate analysis, CTC-d0 >= 5 vs CTC-d0=0-4 was significantly associated with poor PFS. Conclusions: This is the first report over the presence of CTCs and their prognostic role in patients with EGFR T790M-positive NSCLC following disease progression on an EGFR TKI. The use of serial CTC evaluation as a surrogate biomarker needs further validation in larger samples of patients.