Table 1 Summary of Phase 3 clinical trial data for T-DM1.
From: Mechanisms of resistance to trastuzumab emtansine (T-DM1) in HER2-positive breast cancer
Trial | Endpoint | Experimental therapy | Control arm | Hazard ratio (95% CI) | Reference |
|---|---|---|---|---|---|
EMILIA (HER2-positive advanced breast cancer previously treated with trastuzumab and a taxane) | |||||
T-DM1 (n = 495) | Lapatinib + capecitabine (n = 496) | ||||
Overall survival | 30.9 months | 25.1 months | 0.65 (0.55–0.77) | ||
Progression-free survival | 9.6 months | 6.4 months | 0.68 (0.55–0.86) | ||
Grade ≥ 3 adverse events | 48% | 60% | |||
TH3RESA (HER2-positive advanced breast cancer previously treated with both trastuzumab and lapatinib in the advanced setting and a taxane in any setting) | |||||
T-DM1 (n = 404) | Physician’s choicea (n = 198) | ||||
Overall survival | 22.7 months | 15.8 months | 0.68 (0.54–0.85) | ||
Progression-free survival | 6.2 months | 3.3 months | 0.53 (0.42–0.66) | ||
Grade ≥ 3 adverse events | 40% | 47% | |||
Treatment exposure-adjusted rate of grade ≥ 3 adverse events | 123.6/100 patient years | 278.4/100 patient years | |||
MARIANNE (HER2-positive advanced breast cancer or previously untreated metastatic breast cancer) | |||||
T-DM1 (n = 367) | Trastuzumab + taxane (n = 365) | ||||
Progression-free survival | 14.1 months | 13.7 months | 0.91 (0.73–1.13)b | ||
Grade ≥ 3 adverse events | 45.4% | 54.1% | |||
Time to decrease in HRQOL | 7.7 months | 3.6 months | |||
T-DM1 + pertuzumab (n = 363) | Trastuzumab + taxane (n = 365) | ||||
Progression-free survival | 15.2 months | 13.7 months | 0.87 (0.69–1.08)b | ||
Grade ≥ 3 adverse events | 46.2% | 54.1% | |||
Time to decrease in HRQOL | 9.0 months | 3.6 months | |||
KRISTINE (HER2-positive breast cancer in the neoadjuvant setting) | |||||
T-DM1 + pertuzumab (n = 223) | Trastuzumab, pertuzumab, docetaxel + carboplatin (n = 221) | ||||
Pathological complete response | 44.3% | 55.7% | |||
Grade ≥ 3 adverse events | 13% | 64% | |||
KATHERINE (HER2-positive early breast cancer with residual invasive disease at surgery after neoadjuvant therapy with trastuzumab and a taxane) | |||||
T-DM1 (n = 743) | Trastuzumab (n = 743) | ||||
Invasive disease-free survival | 87.8% | 77.8% | 0.50 (0.39–0.64) | ||
Freedom from distant recurrence | 89.5% | 83.7% | 0.60 (0.45–0.79) | ||
Overall survival | 94.3% | 92.5% | 0.70 (0.47–1.05) | ||
Grade ≥ 3 adverse events | 15.4% | 25.7% | |||
