EGFRi , immune checkpoint inhibitor toxicities Flashcards
EGFR main toxicities include
diarrhea
acneiform rash
EGFR diarrhea most likely will occur within
first 4 wks after starting
mechanism of EGFR med diarrhea
unclear but primarily secretory
EGFRi diarrhea is usually grade
1-2
↑ ≤4 stools/day over baseline
grade 1
↑ 4-6 stools/day over baseline
grade 2
↑ 7 or more stools/ day over baseline, incontinence, hospitalization indicated, limits self care activities of daily living
grade 3
treatment for grade 1 EGFRi diarrhea
hydrate
start loperamide 4mg ASAP, 2mg after each loose bowel until BM stops for 12 hrs
treatment for grade 2 EGFRi diarrhea
loperamide as grade 1
if does not improve in 48hrs, hold EGFRi and restart once settled to grade 1 (can consider reducing dose)
treatment for grade 3 EGFRi diarrhea
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
when should EGFRi be stopped permanently due to diarrhea AE
if grade 3 doesn’t resolve to grade 1 by 14 days of holding med
why do EGFRi cause acneiform rashes
Epidermal growth factor (EGF) and EGF receptor play essential role in wound healing through stimulating epidermal and dermal regeneration
rank the following EGFRi for acneiform rash risk
cetuximab, osimertinib, afatinib, pantumumab
afatinib > cetuximab > osimertinib >panitumumab
does acneiform rash respond to OTC acne products
no
acneiform rash from EGFRi usually start within ______, peaks at ____, then regresses with continuation of therapy
1-2wks
2-4wks
Sensory disturbances with erythema and edema phase + wk
grade1
wk 0-1
papulopustular eruptions phase + wk
phase 2
wk 1-3
crusting phase + wk
phase 3
wk 3-5
erythema telangiectasias phase + wk
phase 4
wk 5-8
does acneiform rash from EGFRi result in permanent scaring?
no
when should acneiform rash resolve after therapy?
within 2mths of d/c
what are some positives of seeing acneiform rash from EGFRi
rash may be accurate surrogate marker of efficacy of anti-EGFR therapy, as well as clinical response of the pt
grade 1 acneiform rash: Papules and/or pustules _____ BSA. may or may not be assoc with sx fo pruritus or tenderness
<10%
grade 1 acneiform rash tx
hydrocortisone 1% + clindamycin cream 2%
grade 2 acneiform rash tx
HC1% + Clinda cream 2% + mino/doxycycline 100mg PO BID F4wks
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
10-30%
pruritus or tenderness
psych
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
> 30%
local superinfection
oral abx
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
any %
extensive superinfection
IV abx
prevents inhibition on dendritic cells, which activate the T cell
is a CTLA4i
ipilimumab
AEs from immunotherapy usually related to
autoimmunity and inflammatory response due to self reactive T cells
AEs from immunotherapy can occur at
any time, even after therapy termination
5 pillars of immunotherapy toxicity management
prevent
anticipate
detect
treat
monitor
3 common AEs from immune modulators
immune mediated dermatitis
pneumonitis
enterocolitis
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
1
when does immune med derm happen
at any time, usually ~wk 3
what is grade 1-2 immune med derm
rash ≤30% skin surface
tx for grade 1-2 immune med derm
Moisturizers
Sun safety
Mod potency topical CS
Oral antihistamines
if persists: consider skin biopsy + withholding CI, add oral prednisone + taper over 1mth when improved
what is a grade 3-4 immune med derm
rash >30% BSA
treatment resistant with high QoL impact
or <10% if skin is sloughing off
tx for grade 3-4 immune med derm
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
med time to immune mod pneumonitis
~12 wks
what is grade 1 pneumonitis
radiographic changes only
tx for grade 1 pneumonitis
Consider withholding CI, pulmonary/ID consult
If improves, resume
If worsens, tx as grade 2/3
what is grade 2 pneumonitis
mild-mod new or worsening cough, chest pain, SOB
what is grade 3/4 pneumonitis
Severe new or worsening cough, chest pain, SOB or hypoxia
Can be life threatening
tx for grade 2 pneumonitis
Refer to oncologist/ team
Hold CI
Prednisone daily
If improves, taper prednisone over at least 1 mth
If worsens, treat as grade 3/4
tx for grade 3/4 pneumonitis
Hospitalize + d/c CI
High dose corticosteroids
If improves to baseline, taper prednisone over at least 6wks
If worsens, consider nonsteroid immunosuppression
when does immune therapy med enterocolitis happen
anytime, including after therapy
usual time entercolotis happens from PD1/PD-L1 i
2-3mths
usual time entercolotis happens from CTLA4i
1-5mths
tx for grade 2 enterocolitis
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
tx for grade 3 enterocollitis
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
