Systemic therapy in metastatic pancreatic adenocarcinoma: current practice and perspectives

Abstract

Major breakthroughs have been achieved in the management of metastatic pancreatic ductal adenocarcinoma (PDAC) with FOLFIRINOX (5-fluorouracil + irinotecan + oxaliplatin) and gemcitabine plus nab-paclitaxel approved as a first-line therapy, although the prognosis is still poor. At progression, patients who maintain a good performance status (PS) can benefit from second-line chemotherapy. To address the concern of achieving tumor control while maintaining a good quality of life, maintenance therapy is a concept that has now emerged. After a FOLFIRINOX induction treatment, maintenance with 5-fluorouracil (5-FU) seems to offer a promising approach. Although not confirmed in large, prospective trials, gemcitabine alone as a maintenance therapy following induction treatment with gemcitabine plus nab-paclitaxel could be an option, while a small subset of patients with a germline mutation of breast cancer gene (BRCA) can benefit from the polyadenosine diphosphate-ribose polymerase (PARP) inhibitor olaparib. The rate of PDAC with molecular alterations that could lead to a specific therapy is up to 25%. The Food and Drug Administration (FDA) recently approved larotrectinib for patients with any tumors harboring a neurotrophic tyrosine receptor kinase (NTRK) gene fusion, and pembrolizumab for patients with a mismatch repair deficiency in a second-line setting, including PDAC. Research focused on targeted therapy and immunotherapy is active and could improve patients' outcomes in the near future.

Keywords: FOLFIRINOX; PARP inhibitors; chemotherapy; maintenance; microsatellite instability; nab-paclitaxel; olaparib; pancreatic carcinoma; pembrolizumab; quality of life.

Figure 1.

Management algorithm proposition for metastatic pancreatic adenocarcinoma. dMMR, mismatch repair deficiency; ECOG PS, performance status Eastern Cooperative Oncology Group; gBRCA, germline BRCA mutation.

Figure 2.

Magnetic resonance imaging of a patient with a metastatic pancreatic adenocarcinoma at baseline (a) and after 6 months FOLFIRINOX chemotherapy (b). After a good response under FOLFIRINOX, the patient underwent maintenance treatment with olaparib.