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Pancreatic CancerA Review

Educational Objective
To review the pathophysiology and clinical management of pancreatic cancer.
1 Credit CME
Abstract

Importance  Pancreatic ductal adenocarcinoma (PDAC) is a relatively uncommon cancer, with approximately 60 430 new diagnoses expected in 2021 in the US. The incidence of PDAC is increasing by 0.5% to 1.0% per year, and it is projected to become the second-leading cause of cancer-related mortality by 2030.

Observations  Effective screening is not available for PDAC, and most patients present with locally advanced (30%-35%) or metastatic (50%-55%) disease at diagnosis. A multidisciplinary management approach is recommended. Localized pancreas cancer includes resectable, borderline resectable (localized and involving major vascular structures), and locally advanced (unresectable) disease based on the degree of arterial and venous involvement by tumor, typically of the superior mesenteric vessels. For patients with resectable disease at presentation (10%-15%), surgery followed by adjuvant chemotherapy with FOLFIRINOX (fluorouracil, irinotecan, leucovorin, oxaliplatin) represents a standard therapeutic approach with an anticipated median overall survival of 54.4 months, compared with 35 months for single-agent gemcitabine (stratified hazard ratio for death, 0.64 [95% CI, 0.48-0.86]; P = .003). Neoadjuvant systemic therapy with or without radiation followed by evaluation for surgery is an accepted treatment approach for resectable and borderline resectable disease. For patients with locally advanced and unresectable disease due to extensive vascular involvement, systemic therapy followed by radiation is an option for definitive locoregional disease control. For patients with advanced (locally advanced and metastatic) PDAC, multiagent chemotherapy regimens, including FOLFIRINOX, gemcitabine/nab-paclitaxel, and nanoliposomal irinotecan/fluorouracil, all have a survival benefit of 2 to 6 months compared with a single-agent gemcitabine. For the 5% to 7% of patients with a BRCA pathogenic germline variant and metastatic PDAC, olaparib, a poly (adenosine diphosphate [ADB]-ribose) polymerase inhibitor, is a maintenance option that improves progression-free survival following initial platinum-based therapy.

Conclusions and Relevance  Approximately 60 000 new cases of PDAC are diagnosed per year, and approximately 50% of patients have advanced disease at diagnosis. The incidence of PDAC is increasing. Currently available cytotoxic therapies for advanced disease are modestly effective. For all patients, multidisciplinary management, comprehensive germline testing, and integrated supportive care are recommended.

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Article Information

Corresponding Author: Eileen M. O’Reilly, MD, Memorial Sloan Kettering Cancer Center, 300 E 66th St, Office 1021, New York, NY 10065 (oreillye@mskcc.org).

Accepted for Publication: July 27, 2021.

Author Contributions: Dr O’Reilly had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: All authors.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: All authors.

Critical revision of the manuscript for important intellectual content: All authors.

Obtained funding: Park, O'Reilly.

Administrative, technical, or material support: Park, O'Reilly.

Supervision: O'Reilly.

Other - involved in writing: Chawla.

Conflict of Interest Disclosures: Dr Park reported receiving grant and research support from Astellas, Gossamer Bio, and Merck and providing consultancy to Ipsen. Dr O'Reilly reported receiving grants and research funding to the institution from Genentech-Roche, Celgene-BMS, BioNTech, Arcus, AstraZeneca, and BioAtla; personal fees for serving on a data and safety monitoring board from Cytomx Therapeutics, Rafael Therapeutics, personal fees from Sobi Consulting, non-financial support from Silenseed Consulting, personal fees from Molecular Templates Consulting, personal fees from Boehringer Ingelheim Consulting, personal fees from BioNTech Consulting, personal fees from Ipsen Consulting, personal fees from Polaris Consulting, and personal fees from Merck Consulting during the conduct of the study; other from Bayer Spouse consulting, other from Celgene/BMS Spouse consulting, other from Genentech-Roche Spouse consulting, and other from Eisai Spouse consulting outside the submitted work. No other disclosures were reported.

Funding/Support: Cancer Center Support Grant P30 CA008748; David M. Rubenstein Center for Pancreas Cancer Research; Paul Calabresi Career Development Award K12 CA184746; Parker Institute for Immunotherapy Pilot Grant; Elsa U. Pardee Foundation Grant.

Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

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