Abstract 383P
Background
We have proposed criteria for early circulating tumor DNA (ctDNA) response evaluations (ctDNA-RECIST) based on ddPCR analysis of ctDNA (Spindler et al. TAM 2023) in solid cancers, which are not validated in patients with advanced pancreatic ductal adenocarcinoma (PDAC). The ctDNA aberrant methylation (AM) marker is a pragmatic ctDNA approach, feasible for clinical implementation. This pilot study aimed to demonstrate the relevance of the ctDNA AM analysis in PDAC and the ctDNA-RECIST criteria for future prospective studies.
Methods
Samples were drawn in EDTA tubes prior to first cycle (baseline (BL)), prior to the second cycle of palliative therapy and at the first imaging evaluation in 36 patients with advanced PDAC in the BIOPAC study (NCT03311776) treated as per clinical practice. Four ml was analyzed for AM of HOXA9 by ddPCR, 5 droplets defined positivity. The ctDNA response criteria were; ctDNA progression defined as an increasing value, where the confidence interval (CI) did not overlap with the baseline upper CI, partial response (PR) as a reduction in ctDNA with CI not overlapping the baseline lower CI. Descriptive statistical analysis and Kaplan Major statistics and log rank test was applied to identify relevance for further investigations.
Results
ctDNA test scored positive at BL in 25% (1 of 4) stage 3 and 75% of stage 4 cases, and ctDNA level was numerically higher in stage 4 (3.0%) compared to stage 3 disease (0.7%) and in patients with liver metastases (p=0.03). Patients with ctDNA BL levels above the median experienced shorter OS (HR=2.27, 95% CI 1.08-4.74), p=0.012). An early ctDNA progression (after first cycle) according to the ctDNA-RECIST implied a very short median OS (134 days) compared to patients with ctDNA stabilization or PR (211 and 364 days, p<0.01). ctDNA-PD was observed in cases with both high and very low concentrations of AM HOXA9 at baseline. The limited sample size did not allow for a multivariate analysis, but none of the analyzed co-parameters influenced the univariate analysis.
Conclusions
This study confirms the relevance of further analysis of ctDNA by HOXA9 and the potential utility of the ctDNA-RECIST criteria in metastatic PDAC. The ctDNA analysis will be used in prospective studies of ctDNA-RECIST in this disease.
Clinical trial identification
NCT03311776.
Legal entity responsible for the study
The authors.
Funding
The Danish Cancer Society.
Disclosure
All authors have declared no conflicts of interest.