Package Insert Flashcards
What type of approval do mBC have for enhertu?
This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
What type of breast cancer patients is enhertu approved for?
ENHERTU is indicated for the treatment of:
- adult patients
- Unresectable or metastatic HER2-positive breast cancer
- who have received two or more prior anti-HER2-based regimens in the metastatic setting.
Describe the enhertu approval for gastric cancer?
ENHERTU is indicated for the treatment of:
- Adult patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma
- Who have received a prior trastuzumab-based regimen.
- Standard approval, not accelerated approval
What are the boxed warnings for enhertu?
Warning: Interstitial Lung Disease and Embryo-fatal toxicity
What are the contraindications for enhertu?
None
How long is the initial infusion time? The subsequent infusion time?
Initial = 90 minutes Subsequent = 30 minutes
How long should patients be on enhertu?
Continue until disease progression or unacceptable toxicity
What is the enhertu dose for breast and gastric/gej patients?
Breast = 5.4 mg/kg Gastric/gej = 6.4 mg/kg
What are the dose modifications for breast cancer?
Initial = 5.4 mg/kg
1st reduction = 4.4 mg/kg
2nd reduction = 3.2 mg/kg
3rd = discontinue
What conditions does table 2 list dose modifications for? (4 total)
ILD, neutropenia, thrombocytopenia, left ventricular dysfunction
What is the corticosteroid treatment that should be considered for grade 1 ILD?
Per §5.1, ≥ 0.5 mg/kg/day prednisolone or equivalent
What is the corticosteroid treatment that should be promptly initiated for grade 2 and above ILD?
Per §5.1, ≥ 1 mg/kg/day prednisolone or equivalent and continue for at least 14 days followed by gradual taper for at least 4 weeks
What metrics are used to diagnose neutropenia?
Neutrophil count less than 1.0 to 0.5 x 109/L = grade 3
What is the definition of febrile neutropenia? What is the treatment modification?
Absolute neutrophil count of less than 1 x109/L and temperature greater than 38.3°C or a sustained temperature of 38°C or greater for more than one hour.
Interrupt until resolved, then reduce by one dose level.
What are the treatment modifications for thrombocytopenia?
Grade 3 (platelets less than 50 to 25 x 109/L)= interrupt dose until grade 1 or less then maintain dose
Grade 4 (platelets less than 25 x 109/L)= interrupt dose until grade 1 or less than reduce dose by one level
What are the treatment modifications for neutropenia?
Grade 3 (less than 1.0 to 0.5 x 109/L) = interrupt dose until resolved to grade 2 or less then maintain dose
Grade 4 (less than 0.5 x 109/L)= interrupt dose until resolved to grade 2 or less then reduce dose by one level
What is the full name for enhertu that is listed on the vial?
ENHERTU (fam-trastuzumab deruxtecan-nxki)
What form does enhertu come in and how does a provider prepare it for a patient?
- Comes in lyophilized powder
- Reconstituted in 5 mL sterile water
- If not used immediately, store the reconstituted vials in a refrigerator at 2˚C to 8˚C (36˚F to 46˚F) for up to 24 hours
What cohort of patients was examined for safety for breast cancer patients? How many?
234 patients, pooled analysis from DB-01 and J101 patients that received at least one dose of 5.4 mg/kg enhertu
How many patients experienced ILD? How many were fatal?
9% had ILD, 2.6% had fatal ILD
How long was the median time to onset for ILD? What was the range?
Median time = 4.1 months
Range = 1.2 - 8.3 months
How many patients experienced a neutrophil count decrease?
62%
What percent of patients experienced grade 3 or 4 neutropenia? How many experienced febrile neutropenia?
16% grade 3 or 4.
1.7% febrile
What percent of patients experienced LVEF decrease?
2 patients, 0.9% (both asymptomatic)
What was the median and range for duration of treatment?
Median duration = 7 months
Range = 0.7 - 31 months
What percent of patients had a dose interruption? (pooled data)
33%
What percent had a dose reduction?
18%
What percent of patients had a permanent discontinutation?
9%
What percent of patients were over age 65? Over the age of 75? (pooled)
65 = 26% 75 = 5%
Use of enhertu in patients with renal impairment?
No data available for severe impairment.
No dose adjustment required for patients with mild or moderate impairment
Use in hepatic impaired patients?
Mild does not need dose adjustment,
Moderate should be closely monitored due to possible toxicity of payload
No data on severe impairment
How is enhertu metabolized in the body?
The humanized HER2 IgG1 monoclonal antibody is expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous IgG
How was enhertu metabolized in vitro?
In vitro, DXd is primarily metabolized by CYP3A4
What % of patients had received prior pertuzumab in DB-01?
66%
What % of patients had HR+ disease in DB-01?
53%
Confirmed ORR in DB-01?
60.3%
% CR
% PR
4.3%,
56%
Median DOR in DB-01?
14.8 months
