Abstract 419P
Background
Detection of persistent ctDNA after curative-intent surgery +/- adjuvant therapy may help identify patients (pts) at high risk for disease recurrence. Most ctDNA MRD assays require tumor sequencing to inform ctDNA detection. We evaluated a plasma-only ctDNA assay incorporating both genomic and epigenomic signatures.
Methods
84 CRC pts undergoing curative intent therapy were evaluated for MRD post completion of definitive therapy. Plasma-derived cfDNA was analyzed using a single sample NGS test (LUNAR, Guardant Health, CA) validated in early stage CRC that integrates genomic and epigenomic cancer signatures. A variant classifier was applied to differentiate tumor-derived from non-tumor derived alterations (alts) in a tumor tissue-uninformed approach.
Results
Of 84 pts assessed, 72 had evaluable plasma post completion of standard of care therapy (surgery only =39; adjuvant therapy (adj) = 33). Pts were stage 0-I (n=9), II (n=20), III (n=39), IV (n=16). Median clinical follow up post completion of therapy was 514 days (d). Plasma was collected a median of 31.5d post completion of treatment. 16 pts had detectable ctDNA post completion of treatment (surgery only or surgery plus adjuvant therapy) and exhibited a median time to recurrence of 177 days vs. not reached in pts with undetectable ctDNA (HR 8.94, p<0.0001). 14/16 of ctDNA positive pts recurred (specificity 95.4%, PPV 87.5%;) vs. 14/56 ctDNA negative pts (NPV 75%; sensitivity 50%). Of 16 ctDNA positive pts, 10 pts were identified by detection of both genomic and epigenomic alts, 5 pts by epigenomic only, and 1 pt by genomic only. Both ctDNA positive pts who had not yet recurred at the time of data analysis had <1 year of clinical follow up, and among patients with at least 1 year clinical follow-up, specificity was 100% (PPV 100%; 14/14). Median time from ctDNA detection to recurrence was 59.5d.
Conclusions
In post-op CRC, a plasma-only integrated genomic and epigenomic assay from a single post therapy plasma sample demonstrated favorable PPV and NPV for MRD. Assessment of epigenomic signatures in cfDNA enhanced MRD detection vs. detection of genomic alterations alone.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
A. Hartwig, A. Jaimovich, V.M. Raymond, A. Talasaz: Shareholder/Stockholder/Stock options, Full/Part-time employment: Guardant Health Inc. R.B. Corcoran: Advisory/Consultancy: Guardant Health. All other authors have declared no conflicts of interest.