Breast Cancer (see Breast Cancer)

General Comments

• Trastuzumab Deruxtecan is Indicated for the Treatment of Adult Patients with Unresectable or Metastatic HER2-Positive Breast Cancer Who Have Received ≥2 Prior Anti-HER2-Based Regimens in the Metastatic Setting

Clinical Efficacy

• DESTINY-Breast03 Phase 3, Multicenter, Open-Label, Randomized Trial of Trastuzumab Deruxtecan vs Trastuzumab Emtansine in Breast Cancer Previously Treated with Trastuzumab and a Taxane (NEJM, 2022) [MEDLINE]: n = 524
  • Trastuzumab Deruxtecan
    • 12 Month Disease-Free Progression was 75.8% (95% CI: 69.8-80.7; P<0.001)
    • 12 Month Survival was 94.1% (95% CI: 90.3-96.4; P<0.001)
    • Any Drug-Related Adverse Events: 98.1%
    • Grade 3/4 Drug-Related Events: 45.1%
    • Drug-Related Interstitial Lung Disease: 10.5% (none were grade 4/5)
  • Trastuzumab Emtansine
    • 12 Month Disease-Free Progression was 34.1% (95% CI: 0.22-0.37; P<0.001)
    • 12 Month Survival was 85.9% (95% CI: 0.36-0.86; P<0.001)
    • Any Drug-Related Adverse Events: 86.6%
    • Grade 3/4 Drug-Related Events: 39.8%
    • Drug-Related Interstitial Lung Disease: 1.9% (none were grade 4/5)

Locally Advanced or Metastatic Gastric Cancer (see Gastric Cancer)

General Comments

• 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

Clinical Efficacy

• XXXXX

Dermatologic Adverse Effects

Alopecia (see Alopecia)

• Epidemiology
  • Occurs in ≥20% of Breast Cancer/Gastric Cancer Cases Treated with Trastuzumab Deruxtecan

Gastrointestinal Adverse Effects

Anorexia (see Anorexia)

• Epidemiology
  • Occurs in ≥20% of Breast Cancer/Gastric Cancer Cases Treated with Trastuzumab Deruxtecan

Constipation (see Constipation)

• Epidemiology
  • Occurs in ≥20% of Breast Cancer/Gastric Cancer Cases Treated with Trastuzumab Deruxtecan

Diarrhea (see Diarrhea)

• Epidemiology
  • Occurs in ≥20% of Breast Cancer/Gastric Cancer Cases Treated with Trastuzumab Deruxtecan

Elevated Liver Function Tests (Transaminitis) (see xxxx)

• Epidemiology
  • Occurs in ≥20% of Breast Cancer/Gastric Cancer Cases Treated with Trastuzumab Deruxtecan

Hyperbilirubinemia (see Hyperbilirubinemia)

• Epidemiology
  • Occurs in ≥20% of Gastric Cancer Cases Treated with Trastuzumab Deruxtecan

Nausea/Vomiting (see Nausea and Vomiting)

• Epidemiology
  • Occurs in ≥20% of Breast Cancer/Gastric Cancer Cases Treated with Trastuzumab Deruxtecan

Hematologic Adverse Effects

Anemia (see Anemia)

• Epidemiology
  • Occurs in ≥20% of Breast Cancer/Gastric Cancer Cases Treated with Trastuzumab Deruxtecan

Leukopenia (see Leukopenia)

• Epidemiology
  • Occurs in ≥20% of Breast Cancer/Gastric Cancer Cases Treated with Trastuzumab Deruxtecan

Thrombocytopenia (see Thrombocytopenia)

• Epidemiology
  • Occurs in ≥20% of Breast Cancer/Gastric Cancer Cases Treated with Trastuzumab Deruxtecan

Neurologic Adverse Effects

Fatigue (see Fatigue)

• Epidemiology
  • Occurs in ≥20% of Breast Cancer/Gastric Cancer Cases Treated with Trastuzumab Deruxtecan

Renal Adverse Effects

Hypokalemia (see Hypokalemia)

• Epidemiology
  • Occurs in ≥20% of Breast Cancer/Gastric Cancer Cases Treated with Trastuzumab Deruxtecan

Pulmonary Adverse Effects

Pneumonitis/Interstitial Lung Disease (ILD) (see Interstitial Lung Disease)

• Epidemiology
  • In DESTINY-Breast03 Trial, Pneumonitis/Interstitial Lung Disease Occurred in 10.5% of the Patients in the Trastuzumab Deruxtecan Group and in 1.9% of Patients in the tTrastuzumab Emtansine Group (NEJM, 2022) [MEDLINE]
    • Only One of These were Grade 4 or 5
• Clinical
  • Cough (see Cough)
  • Dyspnea (see Dyspnea)
• Treatment
  • XXXXXX

Other Adverse Effects

Fever (see Fever)

• Epidemiology
  • Occurs in ≥20% of Gastric Cancer Cases Treated with Trastuzumab Deruxtecan