Systemic Clinical Cancer Treatment (1)

Question 1

Give examples of loco-regional therapies

Answer 1

Surgery

Radiotherapy

Question 2

What are systemic medicines?

Answer 2

Cancer medicines

Question 3

Why is systemic cancer therapy important?

Answer 3

Most patients have metastasis already at the time of diagnosis
Loco-regional therapies cannot target these

Question 4

How big does a tumour have to be to be detected clinically?

Answer 4

~2cm

Question 5

How big does a tumour have to be to be treated with radiotherapy?

Answer 5

~1cm

Question 6

What is it called if the tumour is below the clinical detection size?

Answer 6

Micrometastatic disease

Question 7

How many cells are in a 1cm tumour mass?

Answer 7

~1 million

Question 8

How many cells are in a 2cm tumour mass?

Answer 8

~1 billion

Question 9

Name the types of systemic therapies

Answer 9

Cytotoxic chemotherapy
Targeted agents
Endocrine therapy
Immunotherapy

Question 10

What is endocrine therapy?

Answer 10

Anti-oestrogen and anti-androgen therapy for hormone driven cancers - breast and prostate

Question 11

Why is combination therapy advantageous?

Answer 11

Decrease the chance of resistance or delays its emergence

Question 12

What is the issue with combination therapy?

Answer 12

Toxicities can be severe

Need to lower dosages

Question 13

What are the two types of endocrine therapies?

Answer 13

Receptor antagonists

Reduce the production of oestrogen and androgen

Question 14

Name examples of endocrine therapy, receptor antagonists

Answer 14

Oestrogen - Tamoxifen

Androgen - Cyproterone

Question 15

Name examples of endocrine therapy, reducing the production of oestrogen and androgen

Answer 15

Gonadotrophin Releasing hormone analogues (oestrogen and androgen) 
Aromatase inhibitors (oestrogen only)

Question 16

Advantages of endocrine therapies

Answer 16

Relatively few side effects

Well tolerated

Question 17

Disadvantages of endocrine therapies

Answer 17

Can take up to 3 months to have a clinically beneficial effect
Long term side effects:
- osteoporosis
- cardiovascular disease

Question 18

Why is osteoporosis a side effect?

Answer 18

Bone mass is dependent on oestrogen and androgens

Question 19

Who may not benefit from endocrine therapies?

Answer 19

People will advanced stage disease who need a fast response

Question 20

What do small molecule drugs end in?

Answer 20

‘-nibs’

Question 21

What do monoclonal antibody drugs end in?

Answer 21

‘-mabs’

Question 22

Name a targeted drug for renal cell carcinoma and hepatocellular carcinoma and how it works

Answer 22

Sunitinib

Anti-angiogenic drugs which target VEGF and VEGFR

Question 23

What are the advantages of targeted drugs?

Answer 23

More effective than chemotherapy
Less side effects
Can be used in combination with chemotherapy without increasing toxicity
Can be used in patients who are resistant to chemotherapy

Question 24

Name a targeted drug which can be used in NSCLC patients who are unfit for chemotherapy

Answer 24

Erlotinib - targets EGFR

Question 25

Name a targeted drug which is used in combination with chemotherapy

Answer 25

Trastuzumab (Herceptin) for HER2+ breast cancer

Question 26

Name a targeted drug which can be used in CRC patients who are resistant to chemotherapy

Answer 26

Cetuximab - targets EGFR

Question 27

What is the new molecular classification of cancer?

Answer 27

Where cancer can be broken up into molecular subgroups, based on biomarkers, and these molecular subgroups tell you what to target

Question 28

What do tumour cells express on their surface?

Answer 28

Neoantigens

Question 29

What are neoantigens important for?

Answer 29

Allowing the immune system to prevent early tumours (immune surveillance)

Question 30

What are clinical immunotherapies?

Answer 30

Immune checkpoint inhibitors - CTLA-4 inhibitors - PD-1/ PD-L1 inhibitors

Question 31

Name a CTLA-4 inhibitor and describe it

Answer 31

Ipilimumab Monoclonal antibody Inhibits CTLA-4 so B7 binds to CD28 (co-stimulatory molecule)

Question 32

Why do tumour cells express Pd-L1 on its surface?

Answer 32

To inhibit T cell activation

Question 33

What increases the effectiveness of immune checkpoint therapies?

Answer 33

High mutational burden

Question 34

Name a PD-1 inhibitor

Answer 34

Pembrolizumab

Question 35

What is the main benefit of immune checkpoint therapy?

Answer 35

The response appears to be long term

Question 36

How long to immune therapies take to be effective?

Answer 36

~6 months | after see tumour growth in this time

Question 37

What auto-immune toxicities are associated with immune checkpoint therapies?

Answer 37

Colitis Pneumonitis Endocrinopathies

Question 38

What is the next steps for immune checkpoint therapies?

Answer 38

Combination therapies Biomarkers New immune checkpoint therapies

Question 39

Why may combining chemotherapies with immune therapies be helpful?

Answer 39

The chemotherapy drugs will cause a response early on and this may remove the lag phase in the beginning

Question 40

What kind of biomarkers could be used for immune checkpoint therapies?

Answer 40

``` Tumour: - tumour mutation burden - PD-L1 immunohistochemistry - Microsatellite instability (MSI) - High Immune infiltrate in tumour - CD8 positive TIL score - Immunoscore - Immune gene expression signature ```

Question 41

What is neoadjuvant therapy?

Answer 41

Having chemotherapy before surgery

Question 42

What is adjuvant therapy?

Answer 42

Having chemotherapy after surgery

Question 43

Who benefits from neoadjuvant and adjuvant therapies?

Answer 43

Patients who are MSI-high -ve