Pharmacology V: small molecule inhibitors

Question 1

Venetoclax: class, indications, toxicities, key points

Answer 1

1. BCL2i
2. AML in >75 yo or w/ comorbidities that prevent intensive chemo
3. Tumor Lysis Syndrome (TLS), BMS
4. TLS when initiating, dose ramp up to reduce risk, strong CYP3A4 (posaconazole) –> reduce dose

Question 2

Idelalisib: class, indications, toxicities, key points

Answer 2

1. PI3Ki
2. CLL in combo w/ rituximab
3. Immune-mediated toxicities, hepatotoxicity, diarrhea, colitis, infection, pneumonitis, intestinal perforation
4. Selective for delta

Question 3

Alpelisib: class, indications, toxicities, key points

Answer 3

1. PI3Ki
2. PI3KCA-mutated, HR+, HER2- advanced or metastatic breast cancer
3. Hyperglycemia (BG, HgbA1c), diarrhea
4. Selective for alpha

Question 4

Ivosidenib: class, indications, toxicities, key points

Answer 4

1. IDH1i
2. IDH1-mutated AML
3. Differentiation syndrome, QTc
4. DS –> hold drug & initiate corticosteroids

Question 5

Enasidenib: class, indications, toxicities, key points

Answer 5

1. IDH2i
2. IDH2-mutated AML
3. DS
4. DS –> hold drug & initiate corticosteroids

Question 6

Ribociclib: class, indications, toxicities, key points

Answer 6

1. CDK4/6i
2. HR+, HER2-, advanced or metastatic breast cancer
3. QTc, N/V, neutropenia

Question 7

Palbociclib: class, indications, toxicities, key points

Answer 7

1. CDK4/6i
2. HR+, HER2-, advanced or metastatic breast cancer
3. Neutropenia

Question 8

Abemaciclib: class, indications, toxicities, key points

Answer 8

1. CDK4/6i
2. HR+, HER2-, advanced or metastatic breast cancer
3. N/V, hepatotoxicity, neutropenia

Question 9

Olaparib: class, indications, toxicities, key points

Answer 9

1. PARPi
2. BRCA-mutated breast (early & metastatic), ovarian, pancreatic, prostate cancer
3. Secondary malignancies (AML, MDS)

Question 10

Talazoparib: class, indications, toxicities, key points

Answer 10

1. PARPi
2. BRCA-mutated metastatic breast cancer
3. Secondary malignancies (AML, MDS)

Question 11

Dabrafenib + Trametinib: class, indications, toxicities, key points

Answer 11

1. BRAF + MEKi
2. BRAF V600E/K mutated melanoma, NSCLC, advanced solid tumors
3. Dermatologic (rash, skin cancer), pyrexia (fever)

Question 12

Encorafenib + Binimetinib: class, indications, toxicities, key points

Answer 12

1. BRAF + MEKi
2. BRAF V600E/K mutated melanoma, NSCLC
3. Dermatologic (rash, skin cancer), pyrexia

Question 13

Vemurafenib + Cobimetinib: class, indications, toxicities, key points

Answer 13

1. BRAF + MEKi
2. BRAF V600E/K mutated melanoma
3. Dermatologic (rash, skin cancer), pyrexia