Table 4.

FDA risk-benefit assessment.

DimensionEvidence and uncertaintiesConclusions and reasons
Analysis of condition
  • Approximately 15%−20% of human breast cancers overexpress the HER2.

  • Local and distant breast cancer recurrence remains a major health concern for patients with HER2-positive EBC.

  • Patients with HER2-positive disease without pCR after preoperative treatment are at increased risk of disease recurrence.

Current treatment options
  • Patients with HER2-positive EBC are recommended to complete a total of 1 year of trastuzumab-containing treatment, regardless of the presence of residual disease after preoperative treatment.

  • There is an unmet medical need to develop therapies for patients with HER2-positive EBC and residual invasive disease after preoperative therapy and surgery.

  • Ado-trastuzumab emtansine demonstrated an improvement in IDFS (HR, 0.50; 95% CI, 0.39–0.64; P < 0.0001) compared with trastuzumab for patients with residual invasive disease following treatment preoperative chemotherapy and HER2-targeted therapy followed by surgery.

  • Evidence of effectiveness was supported by a statistically significant and clinically meaningful improvement in IDFS.

Risk and risk management
  • AEs, SAEs, and dose modifications were more common with ado-trastuzumab emtansine.

  • The most common NCI CTCAE Grade ≥3 AEs (>2%) were thrombocytopenia and hypertension.

  • Two new AEs included in the United States Package Insert (USPI) include radiation pneumonitis and blood bilirubin increased.

  • The safety profile of ado-trastuzumab emtansine is acceptable for the intended population, and manageable with current labeling and routine oncology care. Warnings and precautions in labeling detail the serious risks of the drug.