Breast Cancer - Cardiotoxicity Flashcards
ASCO Risk Factors for Cardiotoxicity
- High-dose anthracycline (i.e., cumulative doxorubicin dose ≥ 250 mg/m2, epirubicin ≥ 600 mg/m2
- High-dose radiotherapy (RT; ≥ 30 Gy) where the heart is in the treatment field
- Lower-dose anthracycline (i.e., doxorubicin < 250 mg/m2, epirubicin < 600 mg/m2) in combination
with lower-dose RT (< 30 Gy) where the heart is in the treatment field - Treatment with lower-dose anthracycline or trastuzumab alone, and presence of any of the following risk factors:
– Multiple CV risk factors (≥ two risk factors), including smoking, hypertension, diabetes, dyslipidemia, and obesity, during or after completion of therapy
– Older age (≥ 60 years) at cancer treatment
– Compromised cardiac function (i.e., borderline low LVEF (50 – 55%), history of myocardial infarction (MI), ≥ moderate valvular heart disease) at any time before or during treatment - Treatment with lower-dose anthracycline followed by trastuzumab (sequential therapy)
CARDIOTOXICITY
Anthracyclines
Risk Factors
- HTN
- Dyslipidemia
- DM
- Age >65
- Fx hx of cardiomyopathy
- High cumulative anthracycline dose
- low normal LVEF (50-54%)
- Hx of CV comorbiditites
CARDIOTOXICITY
Anthracyclines
Acute
- Occurs immediately after a single dose or course of therapy with an anthracycline
- Uncommon and transient
- May involve abnormal ECG findings, including QT-interval prolongation, ST-T wave changes, and arrhythmias
- Rarely, CHF and/or pericarditis are observed
- May be caused by an inflammatory response
- Not related to cumulative dose
CARDIOTOXICITY
Anthracyclines
CHRONIC
- Usually w/i a year of receiving anthracycline
- Rapid onset and progression
- more common and life threatening
- Relative to cumulative dose
- Can be resistant to treatment
CARDIOTOXICITY
Anthracyclines
Dexrazoxane
Approved for use in metastatic breast cancer patients who have received cumulative dose >300mg/m2 of doxorubicin
NOT recommended for use in adjuvant setting
- Dosed in 10:1 ratio (dexrazoxane to doxorubicin)
- Doxorubicin must be administered w/i 15-30 minutes of dexrazoxane
CARDIOTOXICITY
Anthracyclines
Recommendations
Any Patient w/ risk factor for cardiotoxicity should have a baseline evaluation of cardiac function ECHO/MUGA
For patients w/ LVEF >50%
Consider repeating after reaching 250-300mg/m2 or equivalent:
- Repeat after reaching 400mg/m2 in patients w/ known risk factors
OR
- Repeat after reaching 450mg/m2 in absence of risk factors
If receiving anthracyclines and dexrazoxane, ASCO guideline on the use of chemo protectants recommend cardiac monitoring for patients who have received cumulative doses of 500mg/m2 and then repeat monitoring after every 50mg/m2 thereafter
CARDIOTOXICITY
Anthracyclines
When to discontinue
Functional signs of cardiotoxicity and/or
Absolute Decrease in LVEF ≥ 10% associated with a decline to a level of <50%
CARDIOTOXICITY
Trastuzumab (all types)
Cardio toxicity is NOT dose related (~5% overall risk)
- appears to be reversible and short lived once discontinued
Cardiomyopathy leading to CHF; clinically similar to anthracycline-induced CHF but reversible with medication despite continuing trastuzumab therapy.
BLACK BOX -> Left ventricular dysfunction
Appears to be responsive to to HF medication therapy however few patients recover to baseline (may recover to LVEF >50% but some damage remains)
CARDIOTOXICITY
Trastuzumab (all types)
Monitoring
Assess LVEF prior to initiation, every 3 months during and upon completion of trastuzumab
Repeat LVEF measurement at 4 week intervals if trastuzumab is held
LVEF measurement every 6 months for at least 2 years following completion of adjuvant trastuzumab
Routine ECHO survellance in patients w/ MBC continuing to receive trastuzumab indefinitely
CARDIOTOXICITY
Trastuzumab (all types)
Management
WITHHOLD trastuzumab for at least 4 weeks for any of the following:
- ≥ 16% absolute decrease in LVEF from baseline
- LVEF below institutional limit of normal and ≥ 10% absolute decrease from baseline
RESUME if LVEF returns to normal limits and absolute decrease from baseline is <= 15% (within 4-8 weeks)
Permanently DISCONTINUE if persistent (>8 weeks) LVEF decline or if suspended ≥ 3 occasions for cardiomyopathy
CARDIOTOXICITY
Pertuzumab
BLACK BOX for Left Ventricular Dysfunction
Asymptomatic LV systolic dysfunction was 3.4% and 6.5% and symptomatic HF was 1.1% pertuzumab/non-anthracycline based chemotherapy and pertuzumab/trastuzumab respectively
CARDIOTOXICITY
Pertuzumab
Management
WITHHOLD Pertuzumab (and trastuzumab) for at least 3 weeks for:
- MBC: LVEF <40% or 40-50% with a fall of ≥ 10% below baseline
- Neoadjuvant/adjuvant: LVEF <50% with a fall of≥ 10% baseline
RESUME if LVEF recovers to:
- MBC: >45% or 40-45% with a fall of <10% baseline
- Neoadjuvant/adjuvant: ≥ 50% or <10% baseline
- Repeat LVEF assessment within approximately 3 weeks.
DISCONTINUE if LVEF has not improved or declined at repeat assessment
CARDITOXICITY
Ado-trastuzumab emtansine (T-DM1)
BLACK BOX for Left Ventricular Dysfunction
CARDITOXICITY
Ado-trastuzumab emtansine (T-DM1)
MONITORING
LVEF should be monitored at baseline and regular intervals (every 3 months) during therapy
CARDITOXICITY
Ado-trastuzumab emtansine (T-DM1)
Management
METASTATIC BREAST CANCER
Metastatic Breast Cancer
- LVEF >45% then continue treatment
T-DM1 should be WITHHELD for at least 3 weeks and LVEF repeated within 3 weeks if:
- LVEF decreases <40% OR
- LVEF decreases to 40-45% with at least 10% decrease from baseline
Treatment can be RESUME if LVEF recovers to >45% or to 40-45% w/ <10% decrease from baseline value within 3 weeks
DISCONTINUE for symptomatic Heart Failure
CARDITOXICITY
Ado-trastuzumab emtansine (T-DM1)
Management
EARLY STAGE BREAST CANCER
LVEF ≥ 50%: CONTINUE TREATMENT
LVEF <45%: HOLD and repeat LVEF w/i 3 weeks. If LVEF <45% confirmed, DISCONTINUE
LVEF 45 to <50% and decrease ≥ 10% from baseline: Hold and repeat LVEF within 3 weeks. If LVEF remains <50% and has not recovered <10% from baseline, DISCONTINUE
LVEF 45 to <50% and decrease is <10% from baseline: continue treatment and repeat LVEF within 3 weeks
CARDITOXICITY
Fam-Trastuzumab Deruxtecan
Monitoring
Assess LVEF prior to initiation and at regular intervals during treatment as clinically indicated
CARDITOXICITY
Fam-Trastuzumab Deruxtecan
Management
LVEF > 45% and absolute decrease from baseline is 10 – 20%: continue treatment
LVEF 40 – 45% and:
- Absolute decrease from baseline < 10%: continue treatment and repeat LVEF assessment within 3 weeks
- Absolute decrease from baseline is 10 – 20%: interrupt treatment and repeat LVEF assessment within 3 weeks. If LVEF has not recovered to within 10% from baseline, permanently discontinue. If LVEF recovers to within 10% from baseline, resume treatment at
the same dose.
LVEF < 40% or absolute decrease from baseline is > 20%: interrupt treatment and repeat LVEF assessment within 3 weeks. If LVEF of < 40% or absolute decrease from baseline of ≥ 20% is confirmed, permanently discontinue
Symptomatic CHF: permanently discontinue
CARDITOXICITY
Margetuximab
MONITORING
Monitor LVEF within 4 prior to and every 3 months during and upon completion of treatment
Monitor LVEF every 4 weeks if margetuximab is withheld for significant LV cardiac dysfunction
CARDITOXICITY
Paclitaxel
Cardiotoxicity usually asymptomatic
- bradyarrhythmias, tachyarrhythmias, atrioventricular and bundle branch blocks, cardiac ischemia, and hypotension
CHF can develop in patients with doxorubicin + paclitaxel
- Appears to be related to doxorubicin total cumulative dose (> 380 mg/m2)
PK interaction between paclitaxel and doxorubicin leads to decreased elimination of doxorubicin
CARDITOXICITY
Albumin-Bound Paclitaxel
Similar Cardiotoxicity as Paclitaxel
Asymptomatic ECG changes including sinus bradycardia and tachycardia, chest pain (rare), supraventricular tachycardia, and cardiac arrest have all been reported
CARDITOXICITY
Docetaxel
Conduction abnormalities, angina, and cardiovascular collapse have been reported, however no direct link between docetaxel and these events has been found
CARDITOXICITY
TAXANES
Treatment
Treat according to standard HF guidelines
