title: Durable Response to Crizotinib in a MET-Amplified, KRAS-Mutated Carcinoma of Unknown Primary.
abstract: BACKGROUND
  Carcinoma of unknown primary (CUP) accounts for 3-5% of all adult solid tumors. An extensive search for the anatomic site of origin is often undertaken in an attempt to tailor systemic treatment, but the latter often has limited efficacy - especially in the setting of an initial treatment failure. Molecularly targeted therapy is an emerging approach that may offer greater efficacy and less toxicity but is most likely to be effective when pairing a tumor harboring a sensitizing genomic alteration with an agent directed at the altered gene product. We report a patient with a CUP harboring a MET amplification with a complete metabolic response to crizotinib despite also harboring a KRAS mutation.
  
  
  METHODS
  Ge-nomic profiling was performed using a clinical next-generation-sequencing-based assay, FoundationOne(®), in a CAP-accredited laboratory certified by Clinical Laboratory Improvement Amendments (Foundation Medicine, Cambridge, Mass., USA).
  
  
  RESULTS
  The CUP harbored both MET amplification (16 copies) and a KRAS G12V mutation. The patient was treated with crizotinib, a MET inhibitor, and has experienced a complete normalization of tumor metabolic activity for more than 19 months.
  
  
  CONCLUSIONS
  Genomic profiling of CUP may reveal clinically meaningful genomic alterations that can guide targeted therapy decision-making. The use of this approach should be studied prospectively as a strategy for the effective treatment of CUP patients and for avoiding resource-intensive workups to identify the tumor site of origin.
authors.affiliation: Foundation Medicine, Cambridge, Mass., USA.
authors.forename: Norma A
authors.initials: NA
authors.lastname: Palma
authors.affiliation: Foundation Medicine, Cambridge, Mass., USA.
authors.forename: Siraj M
authors.initials: SM
authors.lastname: Ali
authors.affiliation: Maryland Oncology Hematology, Columbia, N.Y., USA.
authors.forename: Jamie
authors.initials: J
authors.lastname: O'Connor
authors.affiliation: Sinai Hospital, Baltimore, Md., USA.
authors.forename: Deepa
authors.initials: D
authors.lastname: Dutta
authors.affiliation: Foundation Medicine, Cambridge, Mass., USA.
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.affiliation: Stanford University School of Medicine, Palo Alto, Calif., USA.
authors.forename: Salil
authors.initials: S
authors.lastname: Soman
authors.affiliation: Foundation Medicine, Cambridge, Mass., USA.
authors.forename: Gary A
authors.initials: GA
authors.lastname: Palmer
authors.affiliation: Foundation Medicine, Cambridge, Mass., USA.
authors.forename: Deborah
authors.initials: D
authors.lastname: Morosini
authors.affiliation: Foundation Medicine, Cambridge, Mass., USA.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Ross
authors.affiliation: Foundation Medicine, Cambridge, Mass., USA.
authors.forename: Doron
authors.initials: D
authors.lastname: Lipson
authors.affiliation: Foundation Medicine, Cambridge, Mass., USA.
authors.forename: Phil J
authors.initials: PJ
authors.lastname: Stephens
authors.affiliation: American Radiology Services, USA.
authors.forename: Mayur
authors.initials: M
authors.lastname: Patel
authors.affiliation: Foundation Medicine, Cambridge, Mass., USA.
authors.forename: Vincent A
authors.initials: VA
authors.lastname: Miller
authors.affiliation: Maryland Oncology Hematology, Columbia, N.Y., USA.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Koutrelakos
keywords: Carcinoma of unknown primary; Crizotinib; KRAS mutation; MET amplification; Next-generation sequencing