AngloCeltic Marker Study in Metastatic Breast Cancer

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Anglo-Celtic Marker Study inMetastatic Breast
Cancer
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Tumour Markers in Breast Cancer What are
they for?

• Is it useful to know when tumour markers rise
  following treatment for early breast cancer?
• Is it useful to know when tumour markers rise in
  individuals on treatment for metastatic breast
  cancer (MBC)?

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In individuals known to have elevated levels of
Ca15-3 or CEA at diagnosis of MBC

• Can using changes in serum markers rather than
  changes in symptoms or imaging evidence of
  progression to direct changes of therapy
• Improve overall survival?
• Reduce costs (particularly imaging)?
• Improve (or harm) patient satisfaction?

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Why ask the question?

• Markers can rise 3-12 months before radiological
  evidence of progression
• Smaller tumour volume may mean more cycling cells
  and higher rate of tumour cell kill
  (Norton-Simon)
• Even if impact of earlier intervention with a
  single agent is small and clinically
  insignificant, repeated earlier interventions may
  summate to a greater effect
• Radiological follow up is expensive and involves
  significant waits in parts of the NHS

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To compare

• Standard management
• Change therapy when new symptoms develop or there
  is imaging evidence of disease progression
• Marker directed management
• Change therapy when serum markers rise

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Eligibility

• Newly diagnosed metastatic breast cancer
• Raised Ca15-3 and/or CEA
• Life expectancy gt 6 months

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Randomisation

• Follow up according to normal practice.
• All Investigations and treatments at discretion
  of responsible clinician
• Marker follow up
• Blinded to numerical values
• Plan to change therapy when pre specified change
  in markers occurs
• Investigations and treatment changes in absence
  of marker changes at discretion of responsible
  clinician

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Marker directed arm

• 2-3 Monthly measurement
• All analyses performed centrally in Edinburgh
  (Cathie Sturgeon)
• Marker rise to gt 2SD above ULN OR 30 gt previous
  measurement change of therapy recommended

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Marker directed arm

• Choice to apply recommendation or not with
  clinician and patient
• Failure to apply will be recorded, but does not
  constitute a protocol violation
• Trial Management Group will monitor and have
  discussions with centres where frequent
  non-compliance occurs

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Anti Cancer Therapies

• No particular endocrine or cytotoxic therapies
  are mandated or excluded
• Anticipate participants may receive 3-7 specific
  therapies over course of trial
• Entry into other therapeutic clinical trials
  permitted

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What about other trials?

• Not currently many national trials in MBC
• Trials of new agents
• Primary outcome usually response rate
• Secondary outcomes
• Time to Progression/treatment failure
• Overall Survival
• Do not usually mandate subsequent treatments or
  forbid subsequent trials
• Plan to permit entry into such trials
• Measure markers but suspend direction for
  duration

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Numbers

• Survival difference of 6 months (2-tailed)
• 1500pts
• Survival difference of 4 months (2-tailed)
• 3000pts
• Equivalence study
• hard to define equivalence
• Bigger numbers would be required.

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Follow Up

• Whole of life or Withdrawal of Consent

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Outcome Measures

• Overall Survival Primary Outcome
• Secondary Outcomes
• Treatment related costs
• Include no of imaging investigations
• No of lines of treatment received

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Substudies

• Quality of Life (Galina Velikova)
• Health Economics/Modelling (James Raftery)
• Opportunity to create model that actually
  reflects practice and patient valuations of
  costs/benefits
• Sample collection for development of new
  biomarkers

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Additional knowledge gains

• Narrative account of how metastatic breast cancer
  is managed now in the UK
• Identify practice differences and make
  exploratory analyses of their impact
• What is median survival following diagnosis of
  metastatic breast cancer today?
• Quality of life at different points through the
  illness (one possible sub-study)

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Current Status

• Beckman Coulter will supply
• all reagents for testing Ca15-3 (BR-Monitor) and
  CEA
• Access System Analyser for testing
• All testing centrally in Edinburgh (Cathie
  Sturgeon)
• Goes to NHS HTA Board in Nov (2nd Round of
  applications)
• Turned down for funding by CTAAC

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Current Status

• Goes to NHS HTA Board in Nov (2nd Round of
  applications)
• Turned down for funding by CTAAC