A recent study published in Scientific Reports investigated the prognostic value of circulating tumor DNA (ctDNA) dynamics in patients with advanced EGFR-mutated non-small cell lung cancer (NSCLC) treated with icotinib. The research, which followed 98 patients over a median of 57.5 months, revealed that the clearance of EGFR mutation ctDNA after icotinib administration is significantly associated with improved progression-free survival (PFS) and overall survival (OS).
Study Design and Patient Population
From January 2017 to November 2018, 98 patients with advanced EGFR-mutated NSCLC were enrolled and received icotinib as their first-line treatment. The study population consisted of 58 females (59.2%) and a median age of 61 years. The majority of patients were never smokers (86%) and had adenocarcinoma (82.7%). Most patients had stage IV NSCLC (93.9%), with 40.8% having brain metastasis and 39.8% having bone metastasis. EGFR Exon 19 deletions (19del) were present in 51% of patients, and EGFR L858R mutations in 49%.
ctDNA Dynamics and Clinical Outcomes
Baseline ctDNA was detectable in 71.4% of patients. After four weeks of icotinib treatment, 45.9% of patients with detectable baseline ctDNA achieved clearance (became undetectable). The study classified patients into three groups: Group A (undetectable ctDNA at baseline and week 4), Group B (detectable at baseline, undetectable at week 4 - clearance), and Group C (detectable at week 4 - non-clearance).
The median PFS was significantly different among the three groups: 12.3 months for Group A, 12.3 months for Group B, and 7.6 months for Group C (P=0.003). Specifically, patients in Group A and Group B had significantly better PFS than those in Group C (HR 0.42, P=0.006 and HR 0.43, P=0.004, respectively). The median OS also varied significantly: 34.0 months for Group A, 38.2 months for Group B, and 12.1 months for Group C (P<0.001). Multivariate analysis confirmed that ctDNA clearance (Group A/B vs. Group C) was an independent prognostic factor for both PFS and OS.
Clinical Significance
These findings suggest that ctDNA clearance during icotinib treatment is a valuable predictive biomarker for treatment efficacy in advanced EGFR-mutated NSCLC. The study highlights the potential of using ctDNA monitoring to guide treatment decisions and improve patient outcomes. According to the researchers, assessing ctDNA dynamics could help identify patients who are more likely to benefit from icotinib and those who may require alternative treatment strategies.
Limitations
The study acknowledges limitations, including the single-arm design and the potential for selection bias. Further prospective, randomized controlled trials are needed to validate these findings and explore the optimal use of ctDNA monitoring in clinical practice.
