Clinical implications of ctDNA for EGFR-TKIs as first-line treatment in NSCLC

Purpose: This study aimed to explore the clinical implications of ctDNA for epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) as the first-line treatment in EGFR-mutated (EGFRm) non-small cell lung cancer (NSCLC) in real-world settings.

Methods: A total of 122 patients with NSCLC who underwent tissue and liquid next generation sequencing (NGS) tests were included. 66 patients with detected EGFR mutation in both tumor-tissue and plasma were included into the EGFR^{t+, p+} group, and 56 patients with EGFR mutation detected only in tumor-tissue were included into the EGFR^{t+, p-} group. The differences in clinical characteristics, concomitant mutations and prognosis between the two groups were compared.

Results: The detection rate of the EGFR^{t+, p+} group was 54.1% (66/122). EGFR^{t+, p+} in the NGS test was particularly relevant to the size of tumors, liver metastasis, bone metastasis and TP53 mutation. In patients with TP53 mutation in ctDNA, the detection rate of EGFR mutation in ctDNA was up to 91.3%. EGFR^{t+, p+} could be an independent prognostic factor for first-line EGFR-TKIs treatment. Combination therapy seems to be a promising approach to improve the outcome for EGFR^{t+, p+} (P = 0.017, HR 0.509 [95% CI 0.288-0.897]). Moreover, the combination of TP53 mutated status and EGFRm status in plasma showed a better completion of risk stratification for PFS (Log-rank P < 0.001).

Conclusions: Co-detection of EGFR mutation in tumor tissue and plasma is an independent prognostic factor for first-line EGFR-TKIs treatment. Moreover, combination therapy could be a promising approach to improve the outcome for these patients.