FAM-TRASTUZUMAB DERUXTECAN-NXKI INJ

Clinical Criteria Summary

Clinically significant cardiovascular disease (baseline Left Ventricular Ejection Fraction < 55% via MUGA or echocardiography; <50% if metastatic disease; uncontrolled hypertension or arrhythmia; myocardial infarction within prior 6 months; CHF NYHA Class 3 or 4)
Cumulative prior anthracycline exposure > 360 mg/m2 of doxorubicin or its equivalent
Interstitial lung disease or pneumonitis
Pregnancy
Lactating
Primary Inclusion Criteria (One must be fulfilled)
HER2-overexpressing (IHC 3+ or FISH amplification ratio > 2.0) breast cancer
HER2-overexpressing gastric or gastroesophageal junction adenocarcinoma
Additional Clinical & Administrative Inclusion Criteria (All must be fulfilled)
Care provided by VA or VA Community Care provider of oncology
Goals of care and role of Palliative Care consult discussed and documented, if appropriate
Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
Reproductive Health & Contraception Requirements (Select if applicable)
For females who can become pregnant: Pregnancy must be excluded prior to receiving therapy
For females who can become pregnant: Counseling provided on potential risks vs. benefits of treatment and use of effective contraception during therapy and for 7 months after the last dose

Known hypersensitivity to fam-trastuzumab deruxtecan or its excipients (L-histidine, sucrose, polysorbate 80)
Clinically significant cardiovascular disease* (Baseline Left Ventricular Ejection Fraction < 50% via MUGA or echocardiography; uncontrolled hypertension or arrhythmia; myocardial infarction within prior 6 months; symptomatic Congestive Heart Failure New York Heart Association Class 2-4)
History of, current, or suspected interstitial lung disease/pneumonitis
Clinically active (untreated and symptomatic) Central Nervous System metastases
Uncontrolled HIV or active hepatitis B or C infection
Absolute Neutrophil Count < 1500/mm3 and/or platelet count < 100,000/mm3
Creatinine clearance < 30 ml/min
Total bilirubin > 3 – 10 times Upper Limit of Normal and any AST
Pregnancy (known pregnancy or positive pregnancy test)
Breastfeeding

Unresectable or metastatic HER2-positive breast cancer with prior anti-HER2-based regimen in metastatic, neoadjuvant, or adjuvant setting
Locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma with prior trastuzumab-based regimen
Unresectable or metastatic HER2-low (IHC 1+ or IHC 2+ and ISH negative) breast cancer with at least one prior line of chemotherapy for metastatic disease or disease recurrence within 6 months of adjuvant chemotherapy

For patients who can become pregnant or have partners who can become pregnant: Counseling provided on potential risks vs. benefits of treatment and use of effective contraception during therapy and for 7 months following the last dose

• Adults with unresectable or metastatic HER2-positive breast cancer who have received at least 2 prior anti-HER2 therapies in the metastatic setting
• Adults with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen

• Breast cancer: 5.4 mg/kg IV once every 3 weeks
• Gastric cancer: 6.4 mg/kg IV once every 3 weeks
• Do NOT substitute for or with trastuzumab, trastuzumab biosimilars, or ado-trastuzumab emtansine

• Interstitial lung disease (ILD) and pneumonitis: Closely monitor for cough, dyspnea, fever, and other new or worsening respiratory symptoms; permanently discontinue in patients with Grade 2 or higher ILD/pneumonitis
• Neutropenia: Monitor CBC at baseline, prior to each dose, and as clinically indicated
• Left Ventricular Dysfunction: Evaluate LVEF at baseline and at regular intervals as clinically indicated; permanently discontinue in symptomatic CHF
• Moderately emetogenic: Ensure appropriate antiemetics are provided to prevent acute and delayed nausea/vomiting

• Embryo-fetal harm: Advise patients of the risk and need for effective contraception
• Contraindications: None