KEY TAKEAWAYS
- The study aimed to investigate how baseline detection and early clearance of EGFR ct-DNA in plasma affect survival outcomes in advanced EGFR-m NSCLC.
- Researchers found that ct-DNA persistence at first follow-up predicts worse PFS and OS.
To determine if circulating tumor DNA (ct-DNA) dynamics of epidermal growth factor receptor (EGFR) mutation in plasma can identify a subset of patients with EGFR-mutant (EGFR-m) non-small cell lung cancer (NSCLC) with inferior survival outcomes, we analyzed and compared survival outcomes among patients with and without baseline presence and early clearance of EGFR ct-DNA in plasma.
A Joel and the team conducted a study involving patients with advanced EGFR-m NSCLC, examining the impact of ct-DNA detection at baseline and its clearance at first follow-up on progression-free survival (PFS) and overall survival (OS).
They performed an inclusive analysis involving 66 patients newly diagnosed with EGFR-m NSCLC. Plasma samples were collected at baseline and at the first response assessment, conducted between 12 and 24 weeks, for ct-DNA extraction. The ct-DNA (EGFR exons 18, 19, 20, and 21) was quantified using droplet digital polymerase chain reaction (dd-PCR) on the QX200 ddPCR system (BioRad, USA). Patients with detectable EGFR ct-DNA at baseline and either undetectable or persistent detectable ct-DNA in follow-up samples were classified as clearers and non-clearers, respectively.
About 53 patients received 1st/2nd generation EGFR tyrosine kinase inhibitors (TKIs), while 13 patients were treated with either a 3rd generation TKI (osimertinib) or chemotherapy plus gefitinib. The baseline ct-DNA-positive group exhibited a higher prevalence of extra thoracic disease (60.4% vs. 48.5%). For the entire cohort, there was no significant difference in median PFS between baseline ct-DNA-negative (13.57 months) and ct-DNA-positive patients (12.32 months) (HR 0.74).
However, a significant improvement in PFS was observed among early ct-DNA clearers compared to non-clearers (12.32 months vs. 9.92 months; HR 0.57). For patients treated with 1st/2nd generation EGFR TKIs, the improvement in median PFS among early ct-DNA clearers versus non-clearers was even more pronounced (11.76 months vs. 6.8 months; HR 0.34).
The study concluded that baseline detection of ct-DNA for EGFR mutations in plasma was not predictive of first-line (1L) PFS but was associated with extra thoracic disease. Persistence of ct-DNA at the first follow-up correlated with worse PFS and OS compared to those who cleared ct-DNA from plasma, particularly among patients treated with 1st/2nd generation EGFR TKIs.
This study was funded by the Department of Science and Technology and the Government of India.
Source: https://pubmed.ncbi.nlm.nih.gov/39183550/
Joel A, Abarna R, Chacko RT, et al. (2024). “Analysis of the effect of baseline detection and early clearance of ct-DNA, on survival outcomes among patients with advanced EGFR-mutant non-small cell lung cancer.” Analýza efektu detekce časné clearance ct-DNA při baseline na přežití u pacientů s pokročilým EGFR mutovaným nemalobuněčným karcinomem plic. Klin Onkol. 2024;38(1):40-49. doi:10.48095/ccko202440
