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Circulating Tumor DNA Predictive of Tumor Response in NSCLC
Measuring circulating tumor DNA (ctDNA) in combination with use of the RECIST criteria may improve the accuracy of tumor response measurements in EGFR-mutant non-small cell lung cancer (NSCLC), according to a hypothesis-generating sub-analysis of the FASTACT-2 trial.
“Both radiologic and ctDNA responses are prognostic of progression-free survival (PFS). Incorporation of ctDNA with RECIST may improve tumor response assessment in EGFR-mutant NSCLC,” explained Peey-Sei Kok, Clinical Trials Centre, University of Sydney, Australia, and co-researchers.
In the FASTACT-2 trial, patients with advanced NSCLC received platinum gemcitabine intercalated with erlotinib or placebo. EGFR mutation was measured by both tumor and plasma ctDNA. Of the original 451 patients in the phase 3 trial, 86 (19.1%) were eligible for analysis.
A total of 73% of patients had detectable ctDNA at baseline. At week 8, 40% had radiologic partial response (PR), 60% had stable disease (SD). Further, 80% had undetectable ctDNA response. In patients who had initial PR and undetectable ctDNA, 93% had ongoing PR subsequently at week 16. The median duration of response was 14.9 months. In patients with SD and undetectable ctDNA at week 8, 28% had radiological PR at week 16.
Amongst those with SD at week 8, there was significantly longer survival for those with undetectable versus detectable ctDNA (PFS HR 0.27, 95% CI 0.13-0.57, p < 0.0001; OS HR 0.40, 95% CI 0.20-0.80, P = 0.009).
However, among those with only PR at week 8, survival outcomes for those with undetectable vs detectable ctDNA were not statistically significant (PFS HR 0.49, 95%CI 0.16-1.48, p = 0.21; OS HR 0.39, 95%CI 0.13-1.19, p = 0.10).
