Targeted Oncology Therapies (copy)

Rituximab - Brand, target, MOA, Key safety concerns

Brand: Rituxan

Target: CD20

MOA: Anti-Cluster of Differentiation (CD) Agents: bind to specific antigens expressed on the cell surface, causing cell death

Safety: Hepatitis B reactivation

Cetuximab - Brand, Target, MOA, Key safety concerns

• Brand: Erbitux

• Target: EGFR gene expression - can only use if KRAS wild type

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

• Safety: Dermatologic toxicity (acneform rash), avoid sunlight, use sunscreen, potentially topical steroids/antibiotics

Trastuzumab - Brand, Target, MOA, Key safety concerns

• Brand: Herceptin

• Target: HER2 overexpression

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

• Safety: Cardiotoxicity (monitor LVEF using echo)

Bevacizumab - Brand, Target, MOA, Key safety concerns

• Brand: Avastin

• Target: none (kinda)

• MOA: Vascular Endothelial Growth Factor (VEGF) Inhibitors: inhibit the growth of blood vessels needed for tumor proliferation

• Safety: Impaired wound healing (avoid 28 hours before or after surgery, thromboembolic events, hemorrhage/fatal bleeding, GI perforation

Pembrolizumab and Nivolumab - Brand, Target, MOA, Key safety concerns

• Brand: Keytruda and Opdivo

• Target: PD1 receptor

• MOA: Programmed Death Receptor-1 (PD-1) Inhibitors: bind to the PD-1 receptor on T-cells to block PD-1 ligands from binding, thereby

  increasing T-cell activation and antitumor response, a type of immunotherapy

• Safety: Immune-mediated toxicities

Ipillumumab - Brand, Target, MOA, Key safety concerns

• Brand: Yervoy

• Target: CTLA-4 receptor

• MOA: Cytotoxic T-Lymphocyte Antigen-4 (CTLA-4) Inhibitor: binds to CTLA-4 receptor, which removes the "brake" from T-cell activation.

  increasing T-cell responsiveness and antitumor response, a type of immunotherapy

• Safety: Immune-mediated toxicities

Imatinib, Dasatinnib, Nilotinib - Brand, Target, MOA, Key safety concerns

• Brand: Gleevec, Sprycel, Tasigna

• Target: BCR-ABL fusion gene

• MOA: BCR-ABL Inhibitors: block tyrosine kinase signaling protein produced by the BCR-ABL fusion gene (Philadelphia chromosome) that causes uncontrolled cell division.

• Safety: Fluid retention, QT prolongation (nilotininib), GI upset

Dabrafenib, Vemurafenib - Brand, Target, MOA, Key safety concerns

• Brand: Tafinlar, Zelboraf

• Target: BRAF V600E or V600 K mutation

• MOA: BRAF Inhibitors: inhibit certain mutated forms of protein kinase BRAF, blocking tumor cell growth

• Safety: New malignancies, QT prolongation

Cobimetinib, Trametinib - Brand, Target, MOA, Key safety concerns

• Brand: Cotellic, Mekinist

• Target: BRAF V600 or V600 K when used in combo with BRAF inhibitor

• MOA: Mitogen-Activated Extracellular Kinase (MEK) 1 and 2 Inhibitors: inhibit MEK, a cell signaling protein downstream from RAF

• Safety: Retinopathy, rhabdomyolysis

Afatinib, Erlotinib - Brand, Target, MOA, Key safety concerns

• Brand: Gilotrif, Tarceva

• Target: EGFR gene mutation (19 del or 21 sub)

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

• Safety: Dermatologic toxicitity (acneiform rash), avoid sunlight, use sunscreen, potentially topical steroids/antibiotics

Why are females at the most risk for breast cancer?

• They produce more estrogen and progesterone than males

• Breast cells on females are more likely to mutate because they are more

What gene mutations can dramatically increase breast cancer incidence?

BRCA1 and BRCA 2 - Normally suppress tumor growth

What drugs can be used for breast cancer prevention?

• Tamoxifen - SERM - Pre- or postmenopausal

• Raloxifene - SERM - ONLY postmenopausal

What is the first line treatment for premenopausal females with breast cancer?

Tamoxifen - prevents estrogen from binding to receptors

Aromatase inhibitors are NOT used

What is the first line treatment for postmenopausal females with breast cancer?

Tamoxifen or an aromatase inhibitor

Tamoxifen - Brand, MOA, Concerns, Safety, Side effects

Brand: Soltamox (oral)

MOA: Selective Estrogen Receptor Modulators (SERMs): compete with estrogen at receptor binding sites in breast and other tissues

Concerns: Prodrug converted via CYP2D6; efficacy is decreased with CYP2D6 inhibitors

Safety: Increases risk of uterine or endometrial cancer and thromboembolic events

Side effects: Hot flashes/night sweats, vaginal bleeding/discharge, decrease bone density

Tamoxifen is teratogenic

Fulvestrant - Brand, MOA, Side effects

Brand: Faslodex (IV only)

MOA: Selective Estrogen Receptor Degrader (SERD): estrogen receptor antagonist that causes receptor downregulation

Side effects: Increased LFTs, injection site pain, hot flashes

Anastrozole - Brand, MOA, Concerns, Side effects

Brand: Arimedex

MOA: Aromatase Inhibitors: block peripheral conversion of androgens to estrogen

Concerns: Higher risk of osteoporosis, high risk of CVD

Side effects: Hot flashes/night sweats, arthralgia/myalgia

What is used for HER2 postive breast cancer treatment?

Trastuzumab or pertuzumab which target HER2 protein

How to identify prostate cancer?

Digital rectal exam or prostate-specific antigen blood test >10 ng/mL

What classes are used to manage prostate cancer?

GnRH antagonist or a GnRH agonist

Antiandrogen

Leuprolide, Goserelin - Brand, MOA, Concerns, Side effects

Brand: Lupron, Zoladex

MOA: Gonadotropin-Releasing Hormone (GRH) Agonists: also referred to as luteinizing hormone-releasing hormone (LHRH) agonists; cause an initial surge in testosterone, followed by a gradual reduction through a negative feedback mechanism

Concerns: Risk of osteoporosis, tumor flare (prevent with concurrent use of antiandrogen)

Side effects: Hot flashes, impotence, gynecomastia, bone pain, QT prolongation

Degrarelix, Relugolix - Brand, MOA, Concerns, Side effects

Brand: Firmagon, Orgovyx

MOA: Gonadotropin-Releasing Hormone (GRH) Antagonists: block GnRH receptors directly causing a rapid decrease in testosterone production

Concerns: NO tumor flare, antiandrogen not needed

Side effects: Hot flashes, QT prolongation

Bicalutamide - Brand, MOA, Contraindications, Side effects

Brand: Casodex

MOA: First generation antiandrogen: competitively inhibit testosterone from binding to prostate cancer cells.

Contraindications: Do not use in females

Side effects: Hot flashes, gynecomastia

Apalutamide, Darolutamide - Brand, MOA, Warnings, Side effects

Brand: Erleada, Nubeqa

MOA: Second-generation antiandrogen: competitively inhibits testosterone from binding to prostate cancer cells.

Warnings: Seizures, myocardial ischemia

Side effects: Hypertension, fatigue, increased LFTs, skin rash

Abiraterone - Brand, MOA, Concerns, Warnings, Side effects

Brand: Zytiga

MOA: Androgen Biosynthesis Inhibitor: interferes with CYP17 enzyme involved in the synthesis of steroid hormones in the testes and adrenal glands to decrease testosterone production.

Concerns: Major CYP3A4 substrate

Warnings: Hepatotoxicity

Side effects: Edema, hypertension, hot flashes, increased TGs