OncoTargets and Therapy (2019-05-01)

Complete response to crizotinib in a metastatic adenocarcinoma of unknown primary harboring MET amplification and NTRK1 co-occurring mutation

  • Yao J,
  • Wang A,
  • Wang X,
  • Zhang L,
  • Zhu Y,
  • Ou Y,
  • Wang Z,
  • Yang Y

Journal volume & issue
Vol. Volume 12
pp. 4261 – 4267

Abstract

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Jing-hao Yao,1 An-sheng Wang,2 Xiao-jing Wang,3,4 Lu Zhang,1 Yue Zhu,1 Yu-rong Ou,5 Zi-shu Wang,1 Yan Yang11Department of Medical Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, People’s Republic of China; 2Department of Thoracic Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, People’s Republic of China; 3Department of Respiration, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, People’s Republic of China; 4Anhui Clinical and Preclinical Key Laboratory of Respiratory Diseases, Bengbu 233004, People’s Republic of China; 5Department of Pathology, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, People’s Republic of ChinaAbstract: Carcinomas of unknown primary (CUPs) have poor prognosis due to the paucity of data on their clinical characteristics and laboratory features, and empirical chemotherapy still remains the critical management for this kind of disease. This study aimed to present the knowledge of treating an elderly man with metastatic adenocarcinoma of unknown primary and also with a history of long-term hypertension and renal cysts. He was identified to harbor mesenchymal-epithelial transition factor (MET) gene amplification and neurotrophic tyrosine receptor kinase 1 (NTRK1) gene co-occurring mutation by targeted next-generation sequencing analysis upon the progression of empirical chemotherapy. He was then treated with a standard dose of crizotinib (250 mg, twice daily), which exhibited a satisfactory complete response (CR) of the targeted lesions after 1 month of treatment. When the number of renal cysts increased and renal inadequacy occurred after treatment for 2 months, crizotinib was reduced to half-dose (250 mg, once daily), and still conferred maintenance of CR for another 6.5 months and good quality life of the patient. These results suggested that treatments based on driver genes rather than primary tumor types could be a promising manipulation for achieving better treatment outcome, and a half-dose of crizotinib might be both effective and tolerable for MET-overexpressed CUPs with underlying renal diseases.Keywords: carcinoma of unknown primary, crizotinib, MET amplification, NTRK1 mutation, renal cyst

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