TY - JOUR
T1 - Targeting the NTRK Fusion Gene in Pancreatic Acinar Cell Carcinoma
T2 - A Case Report and Review of the Literature
AU - Gupta, Medhavi
AU - Sherrow, Christopher
AU - Krone, Maghan E.
AU - Blais, Edik M.
AU - Pishvaian, Michael J.
AU - Iii, Emanuel F.Petricoin
AU - Matrisian, Lynn M.
AU - Dearbeloa, Patricia
AU - Gregory, Gary
AU - Brown, Alyson
AU - Zalewski, Olivia
AU - Prinzing, Gillian
AU - Roche, Charles
AU - Kanehira, Kazunori
AU - Mukherjee, Sarbajit
AU - Iyer, Renuka
AU - Fountzilas, Christos
N1 - Funding Information:
The authors acknowledge the American Association for Cancer Research and its financial and material support in the development of the American Association for Cancer Research Project GENIE registry and members of the consortium for their commitment to data sharing. Interpretations are the responsibility of study authors. The authors also acknowledge the Roswell Park Comprehensive Cancer Center core grant: NCI support grant P30CA016056.
Funding Information:
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.
Publisher Copyright:
© 2021 Harborside Press. All rights reserved.
PY - 2021/1
Y1 - 2021/1
N2 - 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 Whitemen, 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. Lowerdose 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.
AB - 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 Whitemen, 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. Lowerdose 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.
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U2 - 10.6004/JNCCN.2020.7641
DO - 10.6004/JNCCN.2020.7641
M3 - Article
C2 - 33406492
AN - SCOPUS:85099759759
SN - 1540-1405
VL - 19
SP - 10
EP - 15
JO - JNCCN Journal of the National Comprehensive Cancer Network
JF - JNCCN Journal of the National Comprehensive Cancer Network
IS - 1
ER -