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Welcome to CME on ReachMD. This episode is part of our MinuteCE curriculum.

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Diagnosis and management of metastatic pancreatic ductal adenocarcinoma. Pancreatic ductal adenocarcinoma, otherwise known as PDAC, is usually diagnosed at an advanced, incurable stage and has an extremely poor prognosis. About 80 to 90% of patients present with unresectable tumors, and only 13% of patients survive for 5 years. It is the third leading cause of mortality in the US, and the seventh leading cause worldwide. Around 1.7% of men and women will be diagnosed with pancreatic cancer at some point during their lifetime.

Early diagnosis is crucial for improving outcomes, yet it remains challenging due to the often silent nature of early stage disease and the nonspecific symptoms that can appear even in advanced cases. The most reported symptom is abdominal pain, with others like weight loss, fatigue, weakness, floating stools, jaundice, and nausea emerging as the disease progresses. Awareness of risk factors is vital for early diagnosis. Modifiable or clinical risk factors include smoking, alcohol use, obesity, dietary choices, and a personal history of chronic pancreatitis or diabetes. Non-modifiable factors comprise age, with most diagnoses occurring between 65 to 74 years, family history, and genetic disorders like Lynch syndrome and germline mutations in BRCA 2, PALB2, and ATM.

Imaging techniques, primarily CT and MRI scans, are the main diagnostic tools for PDAC. Although no definitive biomarkers exist for early detection, carbohydrate antigen 19-9 and carcinoembryonic antigen can assist with diagnosis in conjunction with imaging. Upon diagnosis, patients should undergo germline genetic testing for inherited mutations. Tumor molecular profiling is recommended for patients with locally advanced or metastatic disease who are candidates for targeted therapies.

Treatment selection hinges on factors such as performance status, comorbidities, and molecular profiles, with systemic chemotherapy being the standard for metastatic PDAC. First-line chemotherapy typically includes FOLFIRINOX, NALIRIFOX, or gemcitabine-based regimens like gemcitabine plus nanoparticle albumin-bound paclitaxel or nab-paclitaxel. The liposomal formulation of irinotecan in NALIRIFOX prevents rapid clearance from the circulation and enhances accumulation in tumors, thereby targeting tumor tissue more effectively and reducing side effects. Patients with germline BRCA mutations who do not progress after platinum-based therapy may qualify for maintenance therapy with a PARP inhibitor.

Second-line therapy options depend on prior treatments and include nal-IRI, which is liposomal irinotecan combined with 5-fluorouracil or 5-FU, and leucovorin or fluoropyrimidine, and gemcitabine-based regimens. Targeted therapy may be an option for patients with certain molecular alterations. For patients with poor performance status and progressive disease, systemic treatment may not be suitable, shifting the focus to palliative care that emphasizes pain management and nutritional support.

In conclusion, pancreatic cancer remains a highly lethal malignancy. Nevertheless, advancements in treatment regimens have improved survival rates. Ongoing efforts in risk assessment and early detection are essential for further enhancing outcomes.

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