CIRCULATING TUMOR CELLS AND T790M IN METASTATIC NON-SMALL-CELL LUNG CANCER PATIENTS WITH EGFR MUTATIONS AND ACQUIRED RESISTANCE TO TKI

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Abstract

Purpose

This study assessed correlations between the presence of circulating tumor cells (CTCs), detection of T790M in organs with metastases or circulating-free DNA (cfDNA), and prognosis in metastatic NSCLC patients with acquired resistance to EGFR-TKI.

Methods

Metastatic NSCLC patients with activating EGFR mutations, who initially responded but subsequently experienced disease progression while on EGFR-TKI treatment, were defined as having acquired resistance. Blood samples were collected after the development of such acquired resistance and CTCs were counted using the CellSearch system (Veridex). At the same time, T790M in affected organs or cfDNA was analyzed with cycleave real-time PCR assay and fragment analysis.

Results

Six men and 14 women with a mean age of 63.5 years (22–84) were enrolled. Histological subtypes were adenocarcinoma in 19 and squamous cell carcinoma in the remaining one. Clinical stages were stage IV in 14 and recurrence with distant metastases after surgical resection in 6. EGFR mutations in tumors at the primary site were G719C in 1, exon 19 deletion in 7, L858R in 10 and G791C + L858R in 2. CTCs were detected in eight (40%). Numbers of CTCs (per 7.5 ml blood) were 1 in four cases and 3, 4, 8 and 24 in one case each. Patients without CTCs survived significantly longer than those with CTCs (more than 1 per 7.5 ml). The mean survival time from the first detection of CTCs was 3.0 months in patients with CTCs and not reached in patients without CTCs (P < 0.001). T790M was detected in six cases (30%). T790M was found in 75% (n = 6/8) of patients without CTCs but in 0% (n = 0/12) of those with CTCs (P < 0.05).

Conclusions

The presence of CTCs was correlated with poorly prognosis and lack of T790M in affected organs or cfDNA. The presence of CTCs was informative for distinguishing patients with or without T790M.

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