Targeted Therapies

Question 1

targeted therapies are ____ or ____

Answer 1

Monoclonal Antibodies or Tyrosine Kinase Inhibitors (small molecule drugs)

Question 2

Q: how to identify pts who will respond to targeted therapies
Q: what is the exception

Answer 2

1. PHARMACOGENOMIC testing must be be performed
2. VEGF inhibitors (vascular endothelial growth factor)

Question 3

They are LARGE proteins that BIND to SPECIFIC ANTIGENS or RECEPTORS on the cell surface and cause cell death

Answer 3

Monoclonal antibodies (mAbs)

Question 4

Biologics can be recognized by the immune system as a foreign substance, mAbs are associated with ____

Answer 4

INFUSION-RELATED REACTIONS

note: typically appear w/in the first few hours of administration and are characterized by fever, flushing, SOB, rash, and sometimes anaphylaxis

Question 5

MOST MABs require the following PREMEDICATIONS:

Answer 5

1. APAP (usually 650 mg PO)
2. Benadryl (IV or PO) or another antihistamine

note: additional meds that may be needed based on the severity of the rxn include H2RAs, steroids, and/or meperidine (for rigors)

Question 6

Representative monoclonal antibody targets examples:

Q: “tu”
Q: “ci”
Q: “li”

Answer 6

1. tumors (riTUximab, ceTUximab)
2. circulatory system (bevaCIzumab)
3. immune system (ipiLImumab, pembroLIzumab)

Question 7

List Anti-Cluster of Differentiation (CD) agents:

MOA: bind to specific antigens expressed on the cell surface, causing cell death

Answer 7

Rituximab (Rituxan)*

Question 8

where does the CD agent Rituximab (Rituxen) target

Answer 8

targets CD20*

Question 9

Key safety concerns for CD agent Rituximab

Answer 9

Hepatitis B reactivation**

Check Heb B panel (hep B surface antigen, hep B core antibody) PRIOR TO TX INITIATION**

note: consider antiviral (entecavir) prophylaxis in select pts

Question 10

List EGFR agents:

MOA: Epidermal Growth Factor Receptor (EGFR) inhibitors, inhibit pathways involved in cellular proliferation, differentiation, and survival

Answer 10

CETUXIMAB (Erbitux)

Panitumumab (Vectibix)

Question 11

Q: what does EGFR Cetuximab target
Q: will it work on KRAS mutation

Answer 11

1. targets EGFR gene expression
2. No, must be KRAS negative (-) wild type to use

Question 12

Key safety concerns for Cetuximab, Panitumumab

Answer 12

1. ACNEIFORM RASH (occurs w/in the 1st two weeks of tx and CORRELATES WITH RESPONSE to THERAPY; i.e. indicates the drug is working)
2. adopt general skin care measures: AVOID SUNLIGHT, use SUNSCREEN, APPLY MOISTURIZER
3. consider prophylactic measures to reduce the risk of skin damage (TOPICAL STEROIDS, ANTIBIOTICS)

Question 13

List HER2 agents

MOA: Human Epidermal Growth Factor Receptor 2 (HER2) inhibitors: bind to extracellular ligand domain of HER2 protein to stop signaling pathways and cell proliferation

Answer 13

TRASTUZUMAB (HERCEPTIN)*

Question 14

where does HER2 trastuzumab target

Answer 14

targets HER2 overexpression*

Question 15

key safety concerns for HER2 trastuzumab

Answer 15

1. CARDIOTOXICITY (cardiomyopathy)*
   monitor LVEF (using ECHOcardiogram or MUGA scan) @ baseline and during tx and s/sx’s of heart failure (edema, SOB)
2. conventional trastuzumab is NOT INCHERCHANGEABLE with biosimilars or emtansine

Question 16

List VEGF agents:

MOA: Vascular Endothelial Growth Factor (VEGF) inhibitors: INHIBIT GROWTH OF BLOOD VESSELS* needed for tumor proliferation

Answer 16

bevaCIzumab (AVASTIN)*

Question 17

Key safety concerns for VEGF inhibitor Bevacizumab (Avastin)

Answer 17

1. IMPAIRED WOUND HEALING* (due to decrease blood flow)
   do NOT administer for 28 days before or after surgery**
2. THROMBOLIC EVENTS* (venous thromboembolism)
3. hemorrhage/ FATAL BLEEDING*
4. GI PERFORATION*

Question 18

List Programmed Death Receptor 1 (PD-1):

MOA PDR-1 inhibitors: bind to the PD-1 receptor on T cells to block PD-1 ligands from binding, thereby increasing T cells activation and anti-tumor response; a type of immunotherapy

Answer 18

1. PembroLIzumab (Keytruda)
2. Nivolumab (Opdivo)

Question 19

Key safety concern for PD-1 inhibitors Pembrolizumab (Keytruda) and Nivolumab (Opdivo)

Answer 19

IMMUNE MEDIATED TOXICITIES* (e.g. endocrinopathies, colitis, hepatotoxicity, pneumonitis, thyroid disorders)

note: Tx typically requires administration of a systemic steroid and/or management of the specific toxicity

Question 20

List Cytotoxic T- Lymphocyte Antigen 4 (CTLA-4):

MOA CTLA-4 inhibitors: binds to CTLA-4 receptor which removes the “break” from T-cells activation, increasing T cell responsiveness and anti-tumor response; a type of immunotherapy

Answer 20

ipilimumab (Yervoy)

Question 21

which classes and associated drugs have a safety concerns for IMMUNE MEDIATED TOXICITIES

Answer 21

1. PD-1 inhibitors (Pembrolizumab, Nivolumab)
2. CTLA-4 inhibitors (Ipilimumab)