Targeting the NTRK Fusion Gene in Pancreatic Acinar Cell Carcinoma: A Case Report and Review of the Literature

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  • 1 Department of Medicine, and
  • 2 Department of Pharmacy, Roswell Park Comprehensive Cancer Center, Buffalo, New York;
  • 3 Perthera, Inc., Holliston, Massachusetts;
  • 4 Department of Medicine, Johns Hopkins University, Baltimore, Maryland;
  • 5 Center for Applied Proteomics and Molecular Medicine, George Mason University, Fairfax, Virginia;
  • 6 The Pancreatic Cancer Action Network, Manhattan Beach, California; and
  • 7 Department of Radiology, and
  • 8 Department of Pathology, Roswell Park Comprehensive Cancer Center, Buffalo, New York.
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Pancreatic acinar cell carcinoma (PACC) is a rare pancreatic exocrine malignancy. Compared with the more common pancreatic ductal adenocarcinoma (PDAC), PACC is more common in younger White men, has earlier stages and a lower mean age (56 vs 70 years) at the time of presentation, and has a better prognosis. In addition to differences in demographic, histologic, and clinical characteristics, PACC has a genomic profile distinct from PDAC, with only rare mutations in TP53, KRAS, and p16 that are commonly found in PDAC. This case report presents a man aged 81 years who presented with a pancreatic body mass with peripancreatic lymph node enlargement. Biopsy of the mass showed acinar cell carcinoma. The patient underwent upfront surgical resection, followed by one cycle of adjuvant gemcitabine, with stoppage of therapy due to poor tolerance. Lower-dose gemcitabine was reintroduced after disease progression 6 months later. Nab-paclitaxel was added to gemcitabine after 6 cycles because of a continued increase in the size of peripancreatic lymph nodes. Combination chemotherapy was stopped after 4 cycles because of further disease progression with new liver metastasis. Molecular testing showed the presence of an SEL1L-NTRK1 fusion. Targeted therapy was started with the oral neurotrophic tropomyosin receptor kinase (NTRK) inhibitor larotrectinib at a dosage of 100 mg twice daily. At the time of writing, the patient has been on therapy for 13 months with an exceptional radiographic response and has not experienced any grade 3 adverse effects. To our knowledge, this is the first clinical report of an NTRK gene fusion in a patient with PACC. This case study highlights the significance of tumor molecular profiling in patients with pancreatic tumors, especially rare histologies.

Submitted May 18, 2020; accepted for publication August 14, 2020.

Disclosures: Dr. Blais, Dr. DeArbeloa, and Mr. Gregory have disclosed that they are employed by and hold leadership positions at Perthera. Dr. Pishvaian has disclosed that he receives grant support from the Pancreatic Cancer Action Network; has received consulting or speaking fees from AstraZeneca/MedImmune, Caris Life Sciences, Celgene, Halozyme, Merck, Merrimack, RenovoRx, and Sirtex Medical; has received travel, accommodation, and expenses support from AstraZeneca/MedImmune, Caris Life Sciences, Halozyme, Merck, Perthera, and Sirtex Medical; receives consulting fees or is a scientific advisor at Perthera; and has received grant/research support from ARMO BioSciences, Bavarian Nordic, Bayer, Bristol-Myers Squibb, Calithera Biosciences, Celgene, Celldex, Curegenix, Fibrogen, Genentech, Gilead Sciences, GlaxoSmithKline, Halozyme, Karyopharm Therapeutics, MedImmune, Merck, Novartis, Regeneron, Pfizer, Pharmacyclics, and Tesaro. Dr. Petricoin has disclosed that he receives consulting fees or is a scientific advisor at Perthera; is a consultant for Avant Diagnostics and Ceres Nanosciences; holds stock in Ceres Nanosciences; and has received grant/research support (institutional) from Genentech, AbbVie, Pfizer, and Mirati. Dr. Matrisian has disclosed that she is employed by and holds a leadership position at the Pancreatic Cancer Action Network. Dr. Mukherjee has disclosed that he has received grant/research support (institutional) from the North American Neuroendocrine Tumor Society. Dr. Iyer has disclosed that she has received grant/research funding from Ipsen, NETRF, and Merck, and has received consulting fees from Merck, Bayer, Novartis, QED Therapeutics, Lexicon, Exelixis, and Advanced Accelerator Applications. Dr. Fountzilas has disclosed that he receives grant/research support (institutional) from NCCN ORP/Taiho Oncology and Merck. The remaining authors have disclosed that they have not received any financial consideration from any person or organization to support the preparation, analysis, results, or discussion of this article. The Pancreatic Cancer Action Network has received support unrelated to this work from the following foundations or companies with an interest in targeted therapy for pancreatic cancer: Skip Viragh Foundation, AbbVie, Amgen, AstraZeneca, Baxter, Biogen Idec, Boston Scientific, Bristol-Myers Squibb, Celgene, Clovis Oncology, Eli Lilly, EMD Serano, FibroGen, Genentech, GlaxoSmithKline, Halozyme, Incyte, Insys, Ipsen, Janssen, Johnson & Johnson, Merrimack, Millennium, Novartis, Pfizer, Takeda, and Verastem.

Correspondence: Medhavi Gupta, MD, Department of Medicine, Roswell Park Comprehensive Cancer Center, Scott Bieler Clinical Science Center, 8th Floor, Elm and Carlton Streets, Buffalo, NY 14263. Email: Medhavi.Gupta@RoswellPark.org
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