KATHERINE (original research)
Trial question
What is the role of trastuzumab emtansine in patients with HER+ early breast cancer with residual invasive disease after neoadjuvant therapy?
Study design
Multi-center
Open label
RCT
Population
1486 patients (1481 female, 5 male).
Inclusion criteria: patients with HER+ early breast cancer who had residual invasive disease in the breast or axilla at surgery after neoadjuvant therapy.
Key exclusion criteria: metastatic breast cancer; history of prior carcinoma in situ; gross residual disease remaining after mastectomy or positive margins after breast-conserving surgery; progressive disease during neoadjuvant therapy; treatment with any anti-cancer investigational drug within 28 days prior to commencing study treatment; history of malignancy within the last 5 years; prior treatment with trastuzumab emtansine; current severe, uncontrolled systemic disease; cardiopulmonary dysfunction; pregnancy or lactation.
Interventions
N=743 trastuzumab emtansine (3.6 mg/kg IV every 3 weeks for 14 cycles).
N=743 trastuzumab alone (6 mg/kg IV every 3 weeks for 14 cycles).
Primary outcome
Invasive disease-free survival at 3 years
88.3%
77%
88.3 %
66.2 %
44.1 %
22.1 %
0.0 %
Trastuzumab
emtansine
Trastuzumab
alone
Significant
increase ▲
NNT = 8
Significant increase in invasive disease-free survival at 3 years (88.3% vs. 77%; HR 2, 95% CI 1.56 to 2.56).
Secondary outcomes
Significant increase in distant recurrence-free survival at 3 years (89.7% vs. 83%; HR 1.67, 95% CI 1.27 to 2.22).
No significant difference in overall survival (94.3% vs. 92.5%; HR 1.43, 95% CI 0.95 to 2.13).
Significant increase in disease-free survival at 3 years (87.4% vs. 76.9%; HR 1.89, 95% CI 1.47 to 2.44).
Safety outcomes
No significant difference in grade ≥ 3 hemorrhage.
Conclusion
In patients with HER+ early breast cancer who had residual invasive disease in the breast or axilla at surgery after neoadjuvant therapy, trastuzumab emtansine was superior to trastuzumab alone with respect to invasive disease-free survival at 3 years.
Reference
Gunter von Minckwitz, Chiun-Sheng Huang, Max S Mano et al. Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer. N Engl J Med. 2019 Feb 14;380(7):617-628.
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