What are the treatment options for metastatic pancreatic adenocarcinoma?

From the Guidelines

Treatment options for metastatic pancreatic adenocarcinoma are limited, but chemotherapy regimens such as FOLFIRINOX, gemcitabine plus nanoparticle albumin-bound paclitaxel, and fluorouracil plus nanoliposomal irinotecan can be effective.

First-line treatment options

• FOLFIRINOX (leucovorin, fluorouracil, irinotecan, and oxaliplatin) can be offered as first-line therapy to patients with a good performance status 1
• Gemcitabine plus nanoparticle albumin-bound paclitaxel is also a viable option for first-line therapy 1

Second-line treatment options

• Gemcitabine plus nanoparticle albumin-bound paclitaxel can be offered as second-line therapy to patients who have received first-line treatment with FOLFIRINOX, have an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 to 1, and a favorable comorbidity profile 1
• Fluorouracil plus nanoliposomal irinotecan can be offered as second-line therapy to patients who have received first-line treatment with gemcitabine plus NAB-paclitaxel, have an ECOG PS of 0 to 1, and a favorable comorbidity profile 1
• Gemcitabine or fluorouracil can be considered as second-line therapy for patients with an ECOG PS of 2 or a comorbidity profile that precludes other regimens 1

Special considerations

• Pembrolizumab is recommended for patients with mismatch repair deficiency or high microsatellite instability tumors 1
• Gemcitabine plus cisplatin may be a good choice for selected patients with disease characterized by hereditary risk factors, such as BRCA or PALB2 mutations 1

From the Research

Treatment Options for Metastatic Pancreatic Adenocarcinoma

The treatment options for metastatic pancreatic adenocarcinoma include:

• Gemcitabine monotherapy, which has been the standard of care for several decades 2
• Combination therapy with gemcitabine plus erlotinib, or with gemcitabine plus nab-paclitaxel, or the multidrug regimen of leucovorin, fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) as first-line chemotherapy 2, 3
• FOLFIRINOX and nab-paclitaxel/gemcitabine as first-line treatment regimens, which have been shown to significantly increase survival in patients with advanced pancreatic cancer 3
• Second-line chemotherapy, which can benefit patients who maintain a good performance status (PS) 4
• Maintenance therapy, which has emerged as a concept to achieve tumor control while maintaining a good quality of life, with options such as 5-fluorouracil (5-FU) maintenance after FOLFIRINOX induction treatment, or gemcitabine alone as a maintenance therapy following induction treatment with gemcitabine plus nab-paclitaxel 4
• Targeted therapy and immunotherapy, which are being researched and may improve patient outcomes in the near future, including the use of polyadenosine diphosphate-ribose polymerase (PARP) inhibitors such as olaparib for patients with a germline mutation of breast cancer gene (BRCA), and the use of larotrectinib for patients with 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 5, 4, 6

Factors Influencing Treatment Selection

The selection of treatment regimen depends on:

• Patient performance status (PS) 3, 4
• Comorbidity 3
• Toxicity 3
• Molecular tumor profiling and other biomarkers, which may provide a rationale for targeted therapies or immunotherapies in the future 5, 4, 6