Longitudinal Monitoring Of ctDNA EGFR Mutation Burden From Urine Correlates With Patient Response To EGFR Tyrosine Kinase Inhibitors: A Case Series
- Tumor-associated EGFR mutations are prevalent in approximately 10-15% of Americans and 35-50% of Asians diagnosed with non-small cell lung cancer (NSCLC).
- Secondary EGFR T790M resistance mutations develop in more than half of treated patients leading to resistance to first and second generation TKI’s and eligibility for third generation TKI’s, specifically targeting this resistance mutation.
- A significant challenge in EGFR mutation assessment is the ability to obtain sufficient tumor tissue for molecular testing.
- Recent work demonstrated that circulating tumor DNA (ctDNA) can be used to identify actionable EGFR gene mutations. Quantitative assessment of systemic ctDNA burden has the potential to assess therapeutic response.
- We report on five patients, who were longitudinally monitored for EGFR mutations using an ultrasensitive and quantitative analytical platform from urine-derived systemic ctDNA in a CLIA-certified, CAP-accredited laboratory.
Patient 4 – Case Example
- 74-year-old Caucasian woman was diagnosed with stage IB NSCLC and underwent complete resection with curative intent.
- She was subsequently found to have recurrent, widely metastatic, EGFR exon 19 deleted NSCLC and was treated with erlotinib.
- She presented with bulky intrathoracic and retroperitoneal progression (Figure 4A).
- Given concern for progression, urinary ctDNA analysis was ordered and confirmed the presence of T790M at 2,426 copies / 105 GEq. Based on these results, she was started on osimertinib.
- She reported rapid clinical improvement at her first 14 day follow up visit.
- This was paralleled by a decline of her urinary mutational ctDNA levels and imaging response at 2.5 months after initiation of osimertinib (Figure 3A).
- Her urinary T790M ctDNA levels were found to decline to 14, 22 and 13 copies per 10 5 GEq at week 14, 19 and 27, respectively (Figure 4B, 4C).
- At her last follow up, she was without clear evidence of disease on CT scan.
Highlighted Tables and Graphs
CT Scan – Intrathoracic and Retroperitoneal Progression
Monitoring Response to Therapy
Urinary ctDNA Levels
- Here we present cases where urinary mutational EGFR assessment aided in the diagnostic workup and clinical management of patients with EGFR mutated NSCLC.
- Recent work demonstrated that EGFR ctDNA can serve as an early indicator of therapeutic response. This can provide valuable information particularly in the setting of late-stage patients treated with experimental therapeutics or in patients progressing on therapy. The non-invasive nature of urinary liquid biopsies allows for repeat testing to capture dynamic changes in systemic ctDNA load. The dynamic changes in ctDNA EGFR systemic load observed in this case series is consistent with previous findings.
- While further work is needed to characterize ctDNA as a formal tool of disease evaluation (e.g. RECIST), dynamic changes in ctDNA load have emerged as potentially viable biomarkers to monitor disease burden and early response to therapy.