Circulating tumour DNA (ctDNA) and circulating tumour cells (CTC) can be used as a ‘liquid biopsy’ to detect gene mutations. Serial blood collection for ctDNA and CTC analyses allows monitoring for treatment response and to understand the mechanisms of acquired resistance. We hypothesised that longitudinal ctDNA and CTC analyses may be used for disease monitoring and could have prognostic significance in patients with advanced EGFR+ NSCLC.
In this prospective study, patients with advanced EGFR+ NSCLC were recruited, with blood and plasma samples collected prior to starting treatment, 4 weeks into treatment and at disease progression. CTCs were enumerated and ddPCR for EGFR activating mutations and the T790M resistance mutation performed on ctDNA. We evaluated the relationship between baseline and decrease in CTC and ctDNA at 4 weeks with clinical outcomes.
A total of 56 plasma specimens from 28 patients were studied. ctDNA was detectable at baseline in 19/28 (68%) patients starting first line EGFR inhibitors. Detectable baseline ctDNA was associated with higher disease burden (p < 0.01). Early disappearance of ctDNA at 4 weeks was associated with radiological response 12 weeks into treatment (p = 0.04) and improved PFS (Median PFS 136 vs 511 days, HR 4.49, p < 0.01) and OS (Median OS 311 days vs NR, HR 5.32, p = 0.01), which remained significant after adjustment for burden of disease. Drop in CTC count at 4 weeks was associated with improved PFS (HR 3.11 p = 0.02) but not OS. Drop in CTC counts at 4 weeks was associated with radiological response, just reaching significance (p = 0.05).
Longitudinal assessment of ctDNA and CTC is an accurate predictor of tumour response and survival outcomes for patients with advanced EGFR+ NSCLC. This offers a potentially cheaper, highly informative and minimally invasive way of monitoring malignancies.
Clinical trial identification
Legal entity responsible for the study
Australian Postgraduate Scholarship, CONCERT top-up scholarship, Lung Foundation Australia.
All authors have declared no conflicts of interest.