76P - Prediction of response to palliative chemotherapy by circulating tumor DNA (ctDNA) kinetics in metastatic pancreatic cancer

Background

Circulating tumor DNA (ctDNA) represents a promising prognostic biomarker for predicting relapse and overall survival in patients with metastatic pancreatic cancer (PC). To test the clinical applicable prognostic value of ctDNA dynamics during treatment, we aimed to detect response to treatment ahead of radiological restaging.

Methods

ctDNA detection using liquid biopsy (ddPCR utilizing KRAS G12/13 (and, if negative, Q61) commercial test kits) was prospectively performed on 70 patients with stage IV PC (i) prior to initiation of systemic chemotherapy and (ii) serially every two weeks until restaging.

Results

Detection rate at baseline was 64.3% (45/70). Reduction of ctDNA levels below 57.9% of its baseline value at week 2 after treatment initiation was significantly predictive for response to treatment (AUC=0.918, sensitivity 91.67%, specificity 100%) and was associated with prolonged overall survival (OS) (5.7 vs. 11.4 months, p=0.006) and progression free survival (PFS) (2.5 vs. 7.7 months, p<0.000) regardless of treatment line. Pretherapeutic ctDNA detection was independently associated with worse OS in patients receiving first line regimen (7 vs. 11.3 months, p=0.046) and regardless of treatment line (11.4 vs. 15.9 months, p=0.045) and associated with worse PFS (3.4 vs. 10.8 months, p=0.018).

Conclusions

The dynamic change of ctDNA during systemic treatment allows the prediction of treatment response and is associated with OS and PFS. Progressive disease was correctly predicted in 100% of patients with preemptive detectable ctDNA after 2 weeks (ctDNA) compared to 12 weeks with current gold standard (CT), enabling change of treatment >80% earlier hereafter.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

H. Rumpold.

Funding

Vinzenzgruppe Austria and Krebshilfe Oberösterreich.

Disclosure

All authors have declared no conflicts of interest.