Toxicities: EGFR Inhibitors Immune Checkpoint Inhibitors Flashcards
EGFR Inhibitors - Diarrhea
– Most likely to occur within the first 4 weeks after initiating treatment
– Mechanism unclear but thought to be primarily secretory
– Usually grade 1-2, but up to 25% of patients will experience grade 3 diarrhea
or higher from EGFR TKIs
mild, grade 1 increase of less than 4 stolls per day over baseline
moderate, increase of 4-6
severe, increase of 7 or more stools
EGFR Inhibitor induced Diarrhea
EGFR Inhibitor diarrhea is managed very similarly to diarrhea
from traditional antineoplastic agents (like capecitabine)
– Drink plenty of fluids
– Avoid high fibre foods
– BRAT diet (bananas, rice, applesauce, toast)
– Avoid dairy (temporary lactose intolerance)
– Loperamide
Management of Diarrhea
from EGFR Inhbitors
for grade 1-4
Grade 1 * Drink clear fluids (maintain good hydration)
* Start loperamide 4 mg asap and 2 mg after each loose bowel movement until
bowel movements cease for 12 hours (maximum debatable, 12-20mg per
day)
Grade 2 * Continue loperamide as above
* If diarrhea does not improve after 48 hours, hold the EGFR TKI. Can restart
EGFR TKI once diarrhea has settled to grade 1 (may consider reduced dose)
Grade 3 * Referral required
* Stool culture to rule out infectious process
* Aggressive fluid replacement (IV fluids)
* Temporarily discontinue EGFR TKI and restart at reduced dose once improved
to grade 1. Permanently discontinue if diarrhea does not improve to grade
within 14 days.
Grade 4 * Life threatening
EGFR Inhibitor TKI and Mab:
Acneiform Rash
- Epidermal growth factor (EGF) and EGF receptor (EGFR) play an essential role
in wound healing through stimulating epidermal and dermal regeneration. - Patients receiving EGFR inhibitors commonly experience an acneiform rash as
an adverse effect - Examples of EGFR inhibitors include: gefitinib, erlotinib, afatinib, osimertinib,
panitumumab, cetuximab
Acneiform rash
– erythema, edema, papulopustular eruptions followed by crusting and
dryness of the skin.
– Looks like “acne” but isn’t like acne in that it can be painful and pruritic
(itchy) and doesn’t respond to OTC acne products
– Very common
* up to 90% of patients on afatinib
* Up to 60% of patients on osimertinib
* Up to 80% of patients on cetuximab
* Up to 50% of patients on panitumumab
– Usually occurs within the first 1-2 weeks of treatment (range 2 days to 6
weeks) peaks after 2–4 weeks, and then slowly regresses with
continuation of therapy
Rash Phases
Phase one Weeks 0-1 Sensory disturbance with erythema and edema
Phase two Weeks 1-3 papulopustular eruptions
Phase three Weeks 3-5 Crusting
Phase four Weeks 5-8 Erythematotelangiectasias (red areas)
- The lesions are usually sterile, however, a secondary bacterial or fungal
infection at the site of the eruption can occur - The severity of the rash waxes and wanes throughout these four phases,
and typically resolves without permanent scarring within two months of
therapy discontinuation
EGFR Inhibitor Acneiform Rash
* Why is this rash so important????
- Positives:
- appearance of a papulopustular rash may be an accurate surrogate marker of the efficacy of
anti-EGFR therapy, as well as for the clinical response of the patient. - Several key clinical trials, along with smaller case series have reported a significant correlation between rash and response to treatment.
if they dont get a rash, doesn’t mean its’ not working - Negatives:
– Can lead to compromised integrity of skin (ie risk of infection from impairment of natural
barrier to infection)
– Patients can experience decreased quality of life
– NON-compliance or therapy discontinuation - Clinicians often want some rash…. But not too much rash!
pt education and monitoring for rash
skin care and hygeine, pat dry
moisturize
avoid sun/heat exposure
don’t pop pustules/rash
avoid OTC anti-acne pdts, benzoyl peroxise ineffective and drying
montior skin closely\
gtade 1 <10% BSA
grade 2 10-30%
grade 3 >30%
grade 4 life threatening
oharmacotx of EGFR inhibitor rash (AB)
what to give fro grade 1-4
Grade 1 (<10% of BSA)
- topical clindamycin 2% + hydrocortisone 1% lotion bid x 4wks
- cannot be hydrocortisone added to Dalacin T solution (contains alcohol and is drying)
- MUST BE CLINDA POWDER + HYDROCORTISONE POWDER
Grade 2 (10-30% of BSA)
- topical clinda + HC AND minocycline/doxycycline 100mg PO BID x 4wks
Grade 3 (>30% of BSA and/or moderate to severe symptoms)
- may need systemic corticosteroids and referral to dermatologist
- may need dose reducation or discontinuation of their EGFR inhibitor tx
Grade 4 (life theratening)
- urgent referral/admission
Patient Education and Monitoring for Acneiform
Rash
- Skin Care and Hygiene
– Wash and clean skin with lukewarm water, gently pat dry
(avoid hot water)
– Apply moisturizers (to intact skin) liberally, gently and
frequently - Avoid perfumed products or alcohol containing products
– Avoid sun exposure and exposure to heat (saunas, steam
rooms hot baths etc) - Avoid popping pimples/pustules/rash
- Avoid topical anti-acne products such as benzoyl
peroxide (doesn’t work and is drying) - Instruct patient to assess their skin daily
- Team to assess patient’s skin at each clinic visit
Immunotherapy Toxicity Management
Background
- Tumors can employ a host of mechanisms to defend themselves
from attack by the immune system
– “Avoiding Immune Destruction” (hallmark of malignancy)
– Tumour cells can take advantage of the “checkpoints” to evade
destruction and death - Modulating these receptors is an approach termed “Immune
Checkpoint Blockade”
– Inhibit the checkpoints Potentiating the bodies own immune system
to act in an anti-tumour fashion
Recap - Immune Checkpoint Inhibitors
Checkpoint Inhibition
- Can cause side effects related to auto-immunity and
inflammatory responses
– Leads to self-reactive T-cells - Although the pharmacologic mechanism of influencing T cell
response is very exciting, it is associated with a different array
of side effects that require close monitoring and different
management strategies
Adverse Effects of Checkpoint Inhibitors
hypophysitis
thyroiditis
adrenal insufficiency enterocolitis
dermatitis
pneumonitis
hepatitis
prancreatitis
motor and sensory neuropathies
arthritis
these are immune mediated adverse effects
immune mediate AE
immune mediated dermatitis
immune mediated enterocolitis
immune mediated organ dysfunction
immune mediated endocrinopathies
Adverse Effects - Checkpoint Inhibitors
- Diverse presentations
- Can be subtle at the beginning
- Can occur at any time
– At beginning, several weeks/months after initiating therapy, after therapy
termination - Can lead to serious autoimmune consequences
- Patients are usually outpatients (ambulatory)
- TAKE HOME MESSAGES:
– Must be vigilant in our patient monitoring to identify and manage these
adverse effects early and quickly
– Patient education is of key importance to empower patients to contact the
team quickly when side effects occur`
5 pillars of immunotx toxicity managmenet
prevent
anticipate - this could happen in time, check up and f/u
detect
treat monitor
