EGFRi , immune checkpoint inhibitor toxicities

Question 1

EGFR main toxicities include

Answer 1

diarrhea
acneiform rash

Question 2

EGFR diarrhea most likely will occur within

Answer 2

first 4 wks after starting

Question 3

mechanism of EGFR med diarrhea

Answer 3

unclear but primarily secretory

Question 4

EGFRi diarrhea is usually grade

Answer 4

1-2

Question 5

↑ ≤4 stools/day over baseline

Answer 5

grade 1

Question 6

↑ 4-6 stools/day over baseline

Answer 6

grade 2

Question 7

↑ 7 or more stools/ day over baseline, incontinence, hospitalization indicated, limits self care activities of daily living

Answer 7

grade 3

Question 8

treatment for grade 1 EGFRi diarrhea

Answer 8

hydrate
start loperamide 4mg ASAP, 2mg after each loose bowel until BM stops for 12 hrs

Question 9

treatment for grade 2 EGFRi diarrhea

Answer 9

loperamide as grade 1
if does not improve in 48hrs, hold EGFRi and restart once settled to grade 1 (can consider reducing dose)

Question 10

treatment for grade 3 EGFRi diarrhea

Answer 10

referral
stool culture to rule out fnectious process
aggressive fluid replacement- with IV
temp stop EGFR and restart at reduced dose once at lvl 1
stop permanently if diarrhea doesn’t improve to grade 1 within 14 days

Question 11

when should EGFRi be stopped permanently due to diarrhea AE

Answer 11

if grade 3 doesn’t resolve to grade 1 by 14 days of holding med

Question 12

why do EGFRi cause acneiform rashes

Answer 12

Epidermal growth factor (EGF) and EGF receptor play essential role in wound healing through stimulating epidermal and dermal regeneration

Question 13

rank the following EGFRi for acneiform rash risk
cetuximab, osimertinib, afatinib, pantumumab

Answer 13

afatinib > cetuximab > osimertinib >panitumumab

Question 14

does acneiform rash respond to OTC acne products

Answer 14

no

Question 15

acneiform rash from EGFRi usually start within ______, peaks at ____, then regresses with continuation of therapy

Answer 15

1-2wks
2-4wks

Question 16

Sensory disturbances with erythema and edema phase + wk

Answer 16

grade1
wk 0-1

Question 17

papulopustular eruptions phase + wk

Answer 17

phase 2
wk 1-3

Question 18

crusting phase + wk

Answer 18

phase 3
wk 3-5

Question 19

erythema telangiectasias phase + wk

Answer 19

phase 4
wk 5-8

Question 20

does acneiform rash from EGFRi result in permanent scaring?

Answer 20

no

Question 21

when should acneiform rash resolve after therapy?

Answer 21

within 2mths of d/c

Question 22

what are some positives of seeing acneiform rash from EGFRi

Answer 22

rash may be accurate surrogate marker of efficacy of anti-EGFR therapy, as well as clinical response of the pt

Question 23

grade 1 acneiform rash: Papules and/or pustules _____ BSA. may or may not be assoc with sx fo pruritus or tenderness

Answer 23

<10%

Question 24

grade 1 acneiform rash tx

Answer 24

hydrocortisone 1% + clindamycin cream 2%

Question 25

grade 2 acneiform rash tx

Answer 25

HC1% + Clinda cream 2% + mino/doxycycline 100mg PO BID F4wks

Question 26

grade 2 acneiform rash: Papules and/or pustules covering ____ BSA, may or may not be assoc w/ sx of _____ Assoc w/ ____ impact + limits instrumental ADL

Answer 26

10-30% pruritus or tenderness psych

Question 27

grade 3 acneiform rash: Papules and/or pustules covering ____ BSA, may or may not be assoc with sx of pruritus or tenderness Assoc w/ ______ - ______ indicated

Answer 27

>30% local superinfection oral abx

Question 28

grade 4 acneiform rash: Papules and/or pustules covering ____ BSA which may or may not be assoc w/ sx pruritus or tenderness Associated with ______with _____indicated Life threatening

Answer 28

any % extensive superinfection IV abx

Question 29

prevents inhibition on dendritic cells, which activate the T cell is a CTLA4i

Answer 29

ipilimumab

Question 30

AEs from immunotherapy usually related to

Answer 30

autoimmunity and inflammatory response due to self reactive T cells

Question 31

AEs from immunotherapy can occur at

Answer 31

any time, even after therapy termination

Question 32

5 pillars of immunotherapy toxicity management

Answer 32

prevent anticipate detect treat monitor

Question 33

3 common AEs from immune modulators

Answer 33

immune mediated dermatitis pneumonitis enterocolitis

Question 34

immune mediated dermatitis is usually 1. mild,very common 2. severe bu rare- SJS, TEN 3. pruritis with rash is rare 4. usually happens after therapy is d/c

Answer 34

1

Question 35

when does immune med derm happen

Answer 35

at any time, usually ~wk 3

Question 36

what is grade 1-2 immune med derm

Answer 36

rash ≤30% skin surface

Question 37

tx for grade 1-2 immune med derm

Answer 37

Moisturizers Sun safety Mod potency topical CS Oral antihistamines if persists: consider skin biopsy + withholding CI, add oral prednisone + taper over 1mth when improved

Question 38

what is a grade 3-4 immune med derm

Answer 38

rash >30% BSA treatment resistant with high QoL impact or <10% if skin is sloughing off

Question 39

tx for grade 3-4 immune med derm

Answer 39

Refer to oncologist ASAP Withhold CI Consider skin biopsy/ derm consult High potency topical CS and/or systemic CS daily until improves to grade 1, then taper over at least 1mth

Question 40

med time to immune mod pneumonitis

Answer 40

~12 wks

Question 41

what is grade 1 pneumonitis

Answer 41

radiographic changes only

Question 42

tx for grade 1 pneumonitis

Answer 42

Consider withholding CI, pulmonary/ID consult If improves, resume If worsens, tx as grade 2/3

Question 43

what is grade 2 pneumonitis

Answer 43

mild-mod new or worsening cough, chest pain, SOB

Question 44

what is grade 3/4 pneumonitis

Answer 44

Severe new or worsening cough, chest pain, SOB or hypoxia Can be life threatening

Question 45

tx for grade 2 pneumonitis

Answer 45

Refer to oncologist/ team Hold CI Prednisone daily If improves, taper prednisone over at least 1 mth If worsens, treat as grade 3/4

Question 46

tx for grade 3/4 pneumonitis

Answer 46

Hospitalize + d/c CI High dose corticosteroids If improves to baseline, taper prednisone over at least 6wks If worsens, consider nonsteroid immunosuppression

Question 47

when does immune therapy med enterocolitis happen

Answer 47

anytime, including after therapy

Question 48

usual time entercolotis happens from PD1/PD-L1 i

Answer 48

2-3mths

Question 49

usual time entercolotis happens from CTLA4i

Answer 49

1-5mths

Question 50

tx for grade 2 enterocolitis

Answer 50

Refer to oncologist/ team- assess need for hospitalization Hold CI IV fluids Rule out infection Antidiarrheal tx, if >3days = start prednisone If improves taper prednisone over at least 1mth

Question 51

tx for grade 3 enterocollitis

Answer 51

May need to hospitalize Gastroenterology consult and consider endoscopy withhold/dc CI High dose corticosteroids- unless bowel perforation If perforated or septic = abx If improves to baseline, taper prednisone over at least 1mth If no response or recurs within 5 days = nonsteroid immunosuppression