Treatment development

Question 1

Micrometastatic disease

Answer 1

10^6 tumour cells

Question 2

Why are microscopic tumour deposits more sensitive to chemotherapy?

Answer 2

• Smaller cell number
• Larger fraction of cells in cycle (higher sensitivity)
• Better drug penetration
• Less heterogeneity

Question 3

Monitoring response

Answer 3

Tumour size
Survival
Quality of life

Question 4

Complete Response (CR)

Answer 4

Disappearance of all target lesions

Question 5

Partial Response (PR)

Answer 5

At least a 30% decrease in the sum of diameters of target lesions

Question 6

Progressive Disease (PD)

Answer 6

At least a 20% increase in the sum of diameters of target lesions

Question 7

Stable Disease (SD)

Answer 7

Other

Question 8

Objective response rate (ORR)

Answer 8

CR + PR

Question 9

What causes pseudoprogression?

Answer 9

Cell invading the tumour during immunotherapy

Question 10

Disease control rate (DCR)

Answer 10

CR + PR + SD

Question 11

Which cells can control cancer many years after immunotherapy has stopped?

Answer 11

T memory cells

Question 12

__________________ testing is not sensitive enough yet to detect early stage tumours and __________________ testing is not precise enough.

Answer 12

ctDNA

fecal occult blood

Question 13

Phase 1 purposes

Answer 13

Assess drug safety
Side effect data
Dose optimisation

Question 14

DLT

Answer 14

drug limiting toxicity

Question 15

Phase 1 volunteers in cancer research

Answer 15

Not healthy

Question 16

How can the BED (biologically effective dose) be measured?

Answer 16

Pharmacokinetics (serum drug levels)

Pharmacodynamic biomarker

Question 17

Phase 2 volunteers in cancer research

Answer 17

50-100

Question 18

Types of phase 2 trials

Answer 18

Randomised
Single arm

Question 19

Phase 2 purposes

Answer 19

Monitor tumour size and survival

Question 20

What do waterfall plots show?

Answer 20

Tumour growth or shrinkage

Question 21

What do swimmers plots show?

Answer 21

Ongoing response after weeks

Question 22

Phase 3 trials

Answer 22

Large randomised trial comparing new drug to standard of care

More details about survival benefit

Question 23

Phase 4

Answer 23

Licensing for clinical use

Question 24

Biomarker

Answer 24

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

Question 25

Predictive biomarker example

Answer 25

Kras for Cetuximab
HER2 for Trastuzamab
BRCA for PARP

Question 26

What can molecular profiling show?

Answer 26

Prognostic Markers

Markers predictive of drug sensitivity/resistance

Markers predictive of adverse events

Question 26

Tumour agnostic

Answer 26

Targeting a driver molecular aberration defines the therapeutic effect, irrespective of tumour-specific biology/anatomy

Question 27

Tumour modulated

Answer 27

Therapeutic effect on a targeted driver molecular aberration is modulated by the tumour-specific biology/anatomy

Question 28

Tumour restricted

Answer 28

Therapeutic effect on a targeted driver molecular aberration is only present in a tumour-specific biology/anatomy context

Question 29

Which phase of a clinical trial are biomarkers normally studied in

Answer 29

3

Question 30

What is the disadvantage of biomarkers?

Answer 30

Usually only a minority subgroup is positive