Table 1.
Landmark studies providing data on T-DM1-induced adverse events
| Study | Phase | Year | Patients, n | Study groups (n) | Primary endpoints | Main finding | Ref. |
|---|---|---|---|---|---|---|---|
| EMILIA | III | 2012 | 991 | T-DM1 (495) vs. lapatinib plus capecitabine (496) | PFS | median PFS T-DM1: 9.6 months vs. median PFS lapatinib plus capecitabine 6.4 months | [4] |
| OS | median OS at the second interim analysis crossed the stopping boundary for efficacy (30.9 vs. 25.1 months) | ||||||
| safety | grade ≥ 3 AEs higher with lapatinib plus capecitabine than with T-DM1 (57% vs. 41%). | ||||||
| TH3RESA | III | 2014 | 602 | T-DM1 (404) vs. physician's choice (198) | PFS | median PFS: T-DM1 6.2 months vs. physician's choice 3.3 months | [5] |
| OS | OS showed a trend favoring T-DM1, but stopping boundary was not crossed | ||||||
| safety profile | lower incidence of grade ≥ 3 AEs with T-DM1 than with physician's choice (8.0% vs. 32%) | ||||||
| WSG-ADAPT | II | 2015 | 375 | T-DM1 (119) vs. T-DM1 plus ET (127) vs. trastuzumab plus ET (129) | pCR rates of each T-DM1 arm (± ET) | pCR 41% T-DM1 and 41.5% T-DM1 plus ET vs. 15.1% trastuzumab plus ET | [9] |
| safety | grade ≥ 3 AE with significant difference between arms (pooled T-DM1 vs. trastuzumab plus ET) | ||||||
| toxicity | very low overall toxicity | ||||||
| KAMILLA | III | 2016 | 2,017 | T-DM1 for CNS metastases at baseline (399) vs. no CNS metastases at baseline (1618) | PFS | median PFS 5.5 months in patients with CNS metastases at baseline vs. 7.9 months in patients with no CNS metastases at baseline | [7] |
| safety profile | grade ≥ 3 AEs higher in patients with CNS metastases at baseline than in patients without CNS metastases at baseline (46% vs. 39%) | ||||||
| KRISTINE | III | 2016 | 432 | T-DM1 plus pertuzumab (223) vs. docetaxel plus carboplatin plus trastuzumab and pertuzumab (219) | pCR rate | pCR rate T-DM1 44.4% vs. docetaxel plus carboplatin plus trastuzumab and pertuzumab 55.7% | [8] |
| safety profile | grade ≥ 3 AEs T-DM1 13.0% vs. docetaxel plus carboplatin plus trastuzumab and pertuzumab 64.4% | ||||||
| MARIANNE | III | 2017 | 1,095 | T-DM1 with pertuzumab (363) or T-DM1 with placebo (367) vs. trastuzumab plus taxane (365) | PFS | median PFS T-DM1 with pertuzumab 15.2 months vs. median PFS T-DM1 14.11 months vs. median trastuzumab plus taxane 13.7 months Addition of pertuzumab to T-DM1 did not improve PFS | [6] |
| safety profile | grade ≥ 3 AEs higher in the trastuzumab plus taxane (54.1%) vs. T-DM1 arm (45.4%) and T-DM1 plus pertuzumab arm (46.2%) |
T-DM1 = trastuzumab emtansine, AE = adverse event, CI = confidence interval, CNS = central nervous system, ET = endocrine therapy, HR = hazard ratio, PFS = progression-free survival, OS = overall survival, pCR = pathological complete response.