Applied precision medicine in metastatic pancreatic ductal adenocarcinoma.

BACKGROUND

Metastatic pancreatic ductal adenocarcinoma (mPDAC) bears a dismal prognosis due to the limited activity of systemic chemotherapy. In our platform for precision medicine, we aim to offer molecular-guided treatments to patients without further standard therapy options.

METHODS

In this single center, real-world retrospective analysis of our platform, we describe the molecular-based therapy approaches used in all 50 patients diagnosed with therapy-refractory mPDAC. A molecular portrait of the tumor specimens was created by next-generation sequencing, immunohistochemistry (IHC), microsatellite instability (MSI) testing, and fluorescence hybridization.

RESULTS

In total, we detected 123 mutations in 50 patients. The five most frequent mutations were ( = 40; 80%), ( = 29; 58%), ( = 8; 16%), ( = 4; 8%), and ( = 4; 8%), which together accounted for 40.2% of all mutations. Two patients had gene fusions, namely, and . IHC detected expression of EGFR, phosphorylated mTOR, and PTEN in 36 (72%), 33 (66%), and 17 patients (34%), respectively. For 14 (28%) of the 50 patients, a targeted therapy was suggested based on the identified molecular targets. The recommended treatments included the mTOR inhibitor everolimus ( = 3), pembrolizumab ( = 3), palbociclib ( = 2), nintedanib ( = 2), and cetuximab, crizotinib, tamoxifen, and the combination of lapatinib and trastuzumab, in one patient each.Finally, five patients received the recommended therapy. Four patients died due to disease progression before radiological assessment. One patient was treated with nintedanib and achieved stable disease for 6 months.

CONCLUSION

Based on our observations, precision medicine approaches are feasible and implementable in clinical routine and may provide molecular-based therapy recommendations for mPDAC.