Lecture 7

Question 1

What are the management for EGFR TKI for diarrhea?

Answer 1

Grade 1-2: Hydration, BRAT diet (bananas, rice, applesauce, toast), and loperamide.
Grade 3: Temporarily stop EGFR TKI, rehydrate, and adjust the dose upon restarting.
Grade 4: Life-threatening; requires immediate discontinuation and intensive management​

Question 2

Provide examples of injectable EGFR TKI ?

Answer 2

colon cancer setting
Panitumumab and cetuximab

Question 3

What is the onset of acneiform rash of EGFR TKI ?

Answer 3

Typically within 1-2 weeks of treatment, peaks around 2-4 weeks, and can last up to 8 weeks.

Question 4

What does the acneiform rash looks like ?

Answer 4

Papulopustular eruptions, often mistaken for acne but can be painful and itchy.

Question 5

What are the PHARM measures if a pt on EGFR has acneiform rash ?

Answer 5

Grade 1( <10%) ( topical clindamycin and hydrocortisone)
-Grade 2 ( 10-30%): typical combo + oral minocycline
-Grade 3 : systemic + stop EGFR

Question 6

What are the recommendations for acneiform rash ?

Answer 6

-Daily assessment from pt
-Avoid OTC anti-acnes with benzoyl peroxide
-Sunscreen

Question 7

What is the most common adverse effect of EGFR inhibitors and when does it typically occur?

Answer 7

Diarrhea, usually within the first 4 weeks of treatment.

Question 8

How should grade 1 EGFR inhibitor-induced diarrhea be managed?

Answer 8

Hydration, BRAT diet, and loperamide (4 mg initially, then 2 mg after each loose stool).

Question 9

What are key skin care recommendations for managing acneiform rash caused by EGFR inhibitors?

Answer 9

A: Use lukewarm water, apply alcohol/perfume-free moisturizers, avoid sun/heat exposure, and avoid popping pustules.

Question 10

What does the presence of a rash indicate in patients treated with EGFR inhibitors?

Answer 10

A: A rash may correlate with treatment efficacy and response.

Question 11

What should be done if a patient develops grade 3 diarrhea on an EGFR inhibitor?

Answer 11

A: Temporarily stop the EGFR TKI, provide aggressive fluid replacement, rule out infection, and restart at a lower dose when symptoms improve.
-Grade 3 : systemic CS + stop EGFR

Question 12

What is the mechanism of action of immune checkpoint inhibitors like pembrolizumab and nivolumab?

Answer 12

A: They block the PD-1 or PD-L1 “brakes” on T-cells, preventing cancer cells from evading immune destruction.

Question 13

What are the common immune-mediated adverse events (IMAE) associated with ICIs?

Answer 13

Dermatitis,
enterocolitis,
Organ failure : pneumonitis, hepatitis, and nephrotitis
endocrinopathies.

Question 14

How is grade 1-2 immune-mediated dermatitis managed?

Answer 14

Use moisturizers, sun protection, and moderate potency topical corticosteroids. For persistent cases, consider oral prednisone and hold the ICI.

Question 15

What are the signs and management steps for immune-mediated pneumonitis?

Answer 15

A: Symptoms include new or worsening cough, chest pain, or shortness of breath. Manage by withholding ICI, initiating corticosteroids, and hospitalizing severe cases.

Question 16

What lab tests are essential for monitoring immune-mediated adverse effects from ICIs?

Answer 16

A: Regular monitoring of TSH, blood glucose, liver function tests (AST, ALT), and renal function (creatinine, electrolytes).

Question 17

Why might antibiotics and PPIs interfere with immune checkpoint inhibitor therapy?

Answer 17

A: They can alter the gut microbiome, potentially reducing the efficacy of ICIs.

Question 18

How is grade 3 acneiform rash managed in a patient on EGFR inhibitors?

Answer 18

A: Hold the EGFR inhibitor, consider skin biopsy, use topical and/or systemic corticosteroids (e.g., prednisone), and resume the EGFR inhibitor after improvement at a reduced dose.

Question 19

What is the role of corticosteroids in managing severe immune-mediated adverse events, and what are the risks of long-term corticosteroid use?

Answer 19

A: Corticosteroids suppress the immune response in severe IMAE but may cause side effects like immunosuppression, hyperglycemia, osteoporosis, and increased risk of infections (requiring prophylaxis for conditions like pneumocystis pneumonia).

Question 20

How should grade 3-4 immune-mediated dermatitis be managed?

Answer 20

A: Withhold the immune checkpoint inhibitor, administer high-potency topical corticosteroids or systemic corticosteroids (e.g., prednisone), and hospitalize the patient if needed.

Question 21

Describe the management of grade 3 or 4 immune-mediated enterocolitis in a patient on pembrolizumab.

Answer 21

A: Hospitalize the patient, stop the ICI, initiate high-dose corticosteroids (e.g., methylprednisolone), consider gastrointestinal consult, and monitor closely for bowel perforation or infection.

Question 22

A patient on pembrolizumab presents with 6-7 loose stools per day, abdominal pain, and mucus in the stool. How should this case be managed?

Answer 22

A: This is likely grade 2-3 immune-mediated enterocolitis. The ICI should be held, IV fluids given for hydration, and corticosteroids (prednisone) initiated. If symptoms worsen, the patient may need to be hospitalized and additional immunosuppressants considered.

Question 23

A patient on nivolumab reports new onset of fatigue, weight gain, and constipation. What should you suspect, and how would you manage it?

Answer 23

A: These symptoms suggest immune-mediated hypothyroidism. Management includes checking thyroid function (TSH), starting levothyroxine if hypothyroidism is confirmed, and potentially holding the ICI until symptoms are stabilized.

Question 24

A patient presents with a mild rash and itching 3 weeks after starting durvalumab. What is the appropriate management?

Answer 24

A: For a grade 1-2 immune-mediated dermatitis, the patient should be managed with moisturizers, sun protection, and moderate potency topical corticosteroids. The ICI can continue with close monitoring unless the rash worsens.

Question 25

What is the treatment approach for a patient who develops immune-mediated pneumonitis on pembrolizumab?

Answer 25

A: Depending on severity, the ICI should be held or permanently discontinued. Mild cases (grade 1) may require corticosteroids and close monitoring, while severe cases (grade 3-4) require hospitalization, high-dose corticosteroids, and possibly additional immunosuppression.

Question 26

What endocrine disorders can be caused by ICIs, and how are they managed?

Answer 26

A: ICIs can cause thyroid dysfunction (hypothyroidism or hyperthyroidism), adrenal insufficiency, and diabetes. Endocrinopathies are managed with hormone replacement (e.g., levothyroxine, insulin) and close monitoring of hormone levels and symptoms.

Question 27

What are the typical symptoms of immune-mediated pneumonitis, and what is the recommended treatment?

Answer 27

A: Symptoms include new or worsening cough, shortness of breath (SOB), and chest pain. Mild cases may require holding the ICI and administering prednisone, while severe cases require hospitalization, high-dose corticosteroids, and possibly additional immunosuppression.