CUP Study: Carcinoma of Unknown Primary


  • No primary cancer can be found in 4-5% of all cancers
  • Cancer without an obvious primary present late with widespread disease
  • Often incurable
  • Expectation is approximately 12 months survival with “best guess” chemotherapy targeting a broad spectrum of possible primary sites
  • Problems with best guess chemotherapy:
  • Not tailored to patient
  • One fit for all philosophy
  • Significant side effects
  • Chemotherapy can KILL - therefore it is not unreasonable for patients to hope the drugs they receive stand a good chance of working

Study Plan 

  • 200 patients with CUP
  • Perform liver biopsy for diagnosis with extra pass for genetic analysis of tumour
  • Research liver biopsy will be genetically analysed by Caris molecular intelligence
  • Twenty commonly altered genes in cancers including HER2, EGFR, P53, k-ras will be analysed for mutations
  • These results dictate the most likely chemotherapy options for the patient
  • Patients will be allocated to "best guess" chemotherapy or gene-directed chemotherapy
  • Control group of patients will be offered best guess chemotherapy until progression
  • If control patients cancer progresses they will be allowed to cross to gene-directed therapy
  • Research group of patients will be offered gene-directed therapy (after clinician has recorded what would have been given if best guess chemotherapy had been used)
  • Research group of patients will be followed until progression
  • Primary end-points: Progression-Free Survival and Overall Survival
  • Secondary end-points: Toxicity of treatment


  • This is the first trial of individualising chemotherapy to fit the patient in the world
  • The potential impact of this is enormous
  • Reduction in toxicity of treatment by withholding drugs that will NOT work
  • Reduction in cost by withholding drugs that DO NOT work
  • Improved survival for all patients with cancer by demonstrating that a tailored individualised aoach is better
  • Withholding drugs if no combination will work to allow patients quality of life and longevity without the harmful side effects of futile treatment