Abstract 340P
Background
Pancreatic ductal adenocarcinoma (PDAC) represents the third leading vause of cancer-related deaths worldwide. Mostly diagnosed at locally advanced or metastatic stage, therapeutic strategies are limited, especially from the second line onwards. Precision medicine currently offers new potentially effective therapeutic options, based on actionable molecular alterations (AMA) according to the ESMO Scale of Clinical Actionability for Molecular Targets (ESCAT). However, access to molecular profiling in pancreatic cancer remains limited and clinical benefits are controversial.
Methods
We conducted a retrospective study on all patients over 18 years of age diagnosed with pancreatic adenocarcinoma and who underwent molecular profiling since 2010 in our institution as part of personalized medicine clinical trials. Molecular analysis was performed on tumor DNA directly from tumor biopsy or peripheral blood samples.
Results
Out of 342 patients who underwent molecular profiling, 69 patients (20%) had an AMA according to the ESCAT classification (I to III), mostly affecting BRCA1 or BRCA2 genes. Four patients had microsatellite instability (MSI). Only 31 out of 69 patients (45%) were able to receive targeted therapy (TT) based on their AMA. Overall survival (OS) of patients who received targeted treatment (group A) was statistically superior to those with AMA who did not receive targeted therapy (group B), and to those without AMA on molecular profiling (group C), with a median OS of 34.89 months for group A compared to 27.07 months for group B and 21.45 months for group C (p=0.03, adjusted for age at diagnosis, disease stage, KRAS status, and number of chemotherapy lines received at the time of molecular analysis). The same trend was observed for overall survival in metastatic stage with a median OS of 32.88 months for group A compared to 17.58 months for group B and 12.94 months for group C (p=0.0004, adjusted for the number of chemotherapy lines received at the time of molecular analysis).
Conclusions
Twenty percent of pancreatic cancers present an AMA that can be treated with TT, and the AMA-TT combination significantly improves overall survival in patients with pancreatic cancer, regardless of the presence of the molecular anomaly.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.