1661P - Precision medicine for pancreatic cancer: A clinical study validating EUS biopsies

Background

Pancreatic cancer (PC) has a high mortality rate and treatment options remain very limited. While there is great appeal in improving patient outcomes by implementing precision medicine in this disease, there are significant barriers including challenges in accessing adequate biopsy material to analyse. Endoscopic ultrasound (EUS) biopsy is a common diagnostic procedure and often the only source of tissue for patients with PC, but the utility of these biopsies to provide high quality biopsy material for clinically relevant molecular profiling remains lacking.

Methods

This study enrolled 135 patients undergoing diagnostic EUS biopsy as standard of care in PC to perform molecular analysis using a commercial 500-gene panel which also provides data on clinically relevant gene fusions, tumour mutation burden (TMB) and microsatellite status. No interventions were provided, but data was analysed and discussed at a Molecular Tumour Board meeting and relevant findings fed back to treating oncologists. Patients were followed for treatment data and survival.

Results

7 patients were unable to be analysed due to a lack of available biopsy material (n=2), withdrawal of consent (n=1) or inadequate QC metrics (n=4). We detected common oncogenes at expected frequencies, with KRAS in 114 (90%), TP53 in 85 (66%), SMAD4 in 13 (10%) and CDKN2A in 11 (9%). Targetable molecular findings were detected in 28 (22%), with RNF43 variants in 11 (9%), high TMB in 10 (8%), BRCA1/2 mutations in 4 (3%), BRAF V600E mutations in 2 (2%), CHEK2 mutation in 1 (1%) and BARD1 mutation in 1 (1%). No microsatellite instability was detected. Median TMB in this cohort was low, as expected, at 3.1Mut/Mb. However, of the 10 patients with high TMB (>10Mut/Mb), 5 of these had markedly hypermutated profiles (TMB >150Mut/Mb). To date, 8 patients (6%) have commenced targeted therapies and survival follow up is ongoing.

Conclusions

This study validates EUS as a reliable and accurate source of biopsy material for clinically relevant tumour profiling and adds to the body of literature highlighting the potential to improve patient outcomes in PC through routine genomic analysis, despite the many challenges.

Clinical trial identification

ACTRN12620000762954.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Victorian Cancer Agency.

Disclosure

All authors have declared no conflicts of interest.