Systemic Therapy in Metastatic Pancreatic Cancer: A Review

The prognosis for pancreatic cancer is still poor, because it is typically identified at an advanced, frequently metastatic stage. Recently, a sequential treatment for metastatic pancreatic ductal adenocarcinoma (mPDAC) has been developed. When the performance status is good, combination chemotherapy regimens such FOLFIRINOX and gemcitabine plus nab-paclitaxel are options for first-line treatment. Gemcitabine monotherapy is a viable choice for patients with lower performance status. Recently, olaparib, a PARP inhibitor, was showed to enhance the amount of time patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) and a BRCA1/-2 germ line mutation can live without their disease worsening. If the initial treatment is unsuccessful, patients should be provided with an alternative treatment option if their ECOG score allows for continued treatment. The combination of 5-FU/FA with nanoliposomal irinotecan has demonstrated better overall survival compared to 5-FU/FA alone. Immune checkpoint drugs like PD1/PD-L1 mAbs are particularly efficacious in malignancies with high microsatellite instability (MSI-h). Limited data in mPDACs suggests that only a part of the already tiny subgroup of MSI-H mPDACs (frequency approximately 1%) appears to benefit substantially from a checkpoint inhibitor treatment. The identification of other subgroups, may further increase therapeutic efficacy.