Treatment development Flashcards
Micrometastatic disease
10^6 tumour cells
Why are microscopic tumour deposits more sensitive to chemotherapy?
- Smaller cell number
- Larger fraction of cells in cycle (higher sensitivity)
- Better drug penetration
- Less heterogeneity
Monitoring response
Tumour size
Survival
Quality of life
Complete Response (CR)
Disappearance of all target lesions
Partial Response (PR)
At least a 30% decrease in the sum of diameters of target lesions
Progressive Disease (PD)
At least a 20% increase in the sum of diameters of target lesions
Stable Disease (SD)
Other
Objective response rate (ORR)
CR + PR
What causes pseudoprogression?
Cell invading the tumour during immunotherapy
Disease control rate (DCR)
CR + PR + SD
Which cells can control cancer many years after immunotherapy has stopped?
T memory cells
__________________ testing is not sensitive enough yet to detect early stage tumours and __________________ testing is not precise enough.
ctDNA
fecal occult blood
Phase 1 purposes
Assess drug safety
Side effect data
Dose optimisation
DLT
drug limiting toxicity
Phase 1 volunteers in cancer research
Not healthy
How can the BED (biologically effective dose) be measured?
Pharmacokinetics (serum drug levels)
Pharmacodynamic biomarker
Phase 2 volunteers in cancer research
50-100
Types of phase 2 trials
Randomised
Single arm
Phase 2 purposes
Monitor tumour size and survival
What do waterfall plots show?
Tumour growth or shrinkage
What do swimmers plots show?
Ongoing response after weeks
Phase 3 trials
Large randomised trial comparing new drug to standard of care
More details about survival benefit
Phase 4
Licensing for clinical use
Biomarker
A parameter that can be objectively measured in a patient or their disease that will provide information regarding a defined biological process or clinical outcome
Predictive biomarker example
Kras for Cetuximab
HER2 for Trastuzamab
BRCA for PARP
What can molecular profiling show?
Prognostic Markers
Markers predictive of drug sensitivity/resistance
Markers predictive of adverse events
Tumour agnostic
Targeting a driver molecular aberration defines the therapeutic effect, irrespective of tumour-specific biology/anatomy
Tumour modulated
Therapeutic effect on a targeted driver molecular aberration is modulated by the tumour-specific biology/anatomy
Tumour restricted
Therapeutic effect on a targeted driver molecular aberration is only present in a tumour-specific biology/anatomy context
Which phase of a clinical trial are biomarkers normally studied in
3
What is the disadvantage of biomarkers?
Usually only a minority subgroup is positive
