97P - Population-based assessment of outcomes in pancreatic ductal adenocarcinoma (PDAC) patients (pts) with pathogenic germline variants (PGVs)

Background

Outcomes in PDAC have historically been poor with median overall survival (mOS) less than 12 months (mo) in advanced cases, though may be better in pts with PGVs in cancer susceptibility genes, particularly those involved in DNA repair with actionable mutations. We evaluated clinical features and survival of PDAC pts with PGVs detected using a universal germline testing approach in the population-based cancer system in British Columbia, Canada.

Methods

All PDAC pts diagnosed from March 2014 to December 2023 with at least one PGV were identified. Diagnoses were confirmed by pathology.

Results

In total, 100 PDAC pts were identified, with PGVs in targetable homologous recombination repair (HRR) genes (BRCA1 n=9, BRCA2 n=35, PALB2 n=4), ATM (n=30), mismatch repair (MMR) genes (MSH6 n=5, MSH2 n=4, PMS2 n=4), CDKN2A (n=11), and other (n=5). Seven pts had 2 PGVs. Median age was 66 (36-89) years, 51% were male, and 26% had pancreatic cancer in a first or second degree relative. At diagnosis, 46 were metastatic and 27 were locally advanced or borderline resectable. Of these, 11 pts did not receive cancer treatments, 2 had radiotherapy (RT) only, and 60 received systemic therapy. Of 27 pts with resectable PDAC, 1 had RT and 26 had surgery: 19 were node positive, 23 started adjuvant therapy, and 18 recurred at a median of 13.1 mo. With median follow up of 24.9 mo in living pts, mOS was 24.9 mo in all treated pts and 17.6 mo in metastatic or locally advanced cases. By genotype, mOS for treated pts with HRR (n=41), MMR (n=12), ATM (n=25), and CDKN2A/other (n=11) PGVs were 25.1, 32.5, 21.9, and 14.2 mo, respectively. Platinum chemotherapy use was more common in HR deficient pts (68% vs 42%, p=0.01), and 2 pts received PARP inhibitors. Two pts with MMR deficiency received immune checkpoint inhibitors.

Conclusions

Our data suggest superior outcomes in PDAC pts with PGVs, with mOS over 24 mo in all pts and 18 mo in advanced cases, along with increased use of genotype-directed therapies. Universal germline testing has important prognostic and treatment implications for PDAC pts in the era of precision medicine, in addition to informing risk-adapted screening and preventative strategies for families, and should be integrated as standard of care.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

D.J. Renouf: Financial Interests, Personal and Institutional, Research Grant: Roche, Bayer, Sanofi, Ipsen. All other authors have declared no conflicts of interest.