Trastuzumab emtansine

The phase III EMILIA or TDM4370g study (NCT00829166) was a randomized open-label trial that enrolled 991 patients with HER2-overexpressing, unresectable, locally advanced or metastatic breast cancer who were previously treated with trastuzumab and a taxane.[73][Level of evidence A1] Patients were randomly assigned to receive either T-DM1 or lapatinib plus capecitabine.

The phase III EMILIA or TDM4370g study (NCT00829166) was a randomized open-label trial that enrolled 991 patients with HER2-overexpressing, unresectable, locally advanced or metastatic breast cancer who were previously treated with trastuzumab and a taxane.[73][Level of evidence A1] Patients were randomly assigned to receive either T-DM1 or lapatinib plus capecitabine.

Median PFS was 9.6 months with T-DM1 versus 6.4 months with lapatinib plus capecitabine (HR, 0.65; 95% CI, 0.55–0.77; P < .001).

The phase III EMILIA or TDM4370g study (NCT00829166) was a randomized open-label trial that enrolled 991 patients with HER2-overexpressing, unresectable, locally advanced or metastatic breast cancer who were previously treated with trastuzumab and a taxane.[73][Level of evidence A1] Patients were randomly assigned to receive either T-DM1 or lapatinib plus capecitabine.

Median OS was longer with T-DM1 versus lapatinib plus capecitabine (29.9 months vs. 25.9 months; HR, 0.75 [95% CI, 0.64–0.88]).[74]

The phase III EMILIA or TDM4370g study (NCT00829166) was a randomized open-label trial that enrolled 991 patients with HER2-overexpressing, unresectable, locally advanced or metastatic breast cancer who were previously treated with trastuzumab and a taxane.[73][Level of evidence A1] Patients were randomly assigned to receive either T-DM1 or lapatinib plus capecitabine.

The incidences of thrombocytopenia and increased serum aminotransferase levels were higher in patients who received T-DM1, whereas the incidences of diarrhea, nausea, vomiting, and palmar-plantar syndrome were higher in patients who received lapatinib plus capecitabine.

Further evidence of T-DM1’s activity in metastatic HER2-overexpressed breast cancer was shown in a randomized phase II study of T-DM1 versus trastuzumab plus docetaxel.[75][Level of evidence B1] This trial randomly assigned 137 women with HER2-overexpressed breast cancer in the first-line metastatic setting.

Further evidence of T-DM1’s activity in metastatic HER2-overexpressed breast cancer was shown in a randomized phase II study of T-DM1 versus trastuzumab plus docetaxel.[75][Level of evidence B1] This trial randomly assigned 137 women with HER2-overexpressed breast cancer in the first-line metastatic setting.

At median follow-up of 14 months, median PFS was 9.2 months with trastuzumab plus docetaxel and 14.2 months with T-DM1 (HR, 0.59; 95% CI, 0.36–0.97).

Further evidence of T-DM1’s activity in metastatic HER2-overexpressed breast cancer was shown in a randomized phase II study of T-DM1 versus trastuzumab plus docetaxel.[75][Level of evidence B1] This trial randomly assigned 137 women with HER2-overexpressed breast cancer in the first-line metastatic setting.

Preliminary OS results were similar between treatment arms.

Further evidence of T-DM1’s activity in metastatic HER2-overexpressed breast cancer was shown in a randomized phase II study of T-DM1 versus trastuzumab plus docetaxel.[75][Level of evidence B1] This trial randomly assigned 137 women with HER2-overexpressed breast cancer in the first-line metastatic setting.

T-DM1 had a favorable safety profile compared with trastuzumab plus docetaxel, with fewer grade 3 adverse events (46.4% vs. 90.9%), adverse events leading to treatment discontinuations (7.2% vs. 40.9%), and serious adverse events (20.3% vs. 25.8%).

Evidence of activity of T-DM1 in heavily pretreated patients with metastatic, HER2-overexpressed breast cancer who had received previous trastuzumab and lapatinib was shown in the randomized phase III TH3RESA study (NCT01419197) of T-DM1 versus physician’s choice of treatment.[76][Level of evidence A1] This trial randomly assigned 602 patients in a 2:1 ratio (404 patients assigned to T-DM1 and 198 patients assigned to physician’s choice) and allowed crossover to T-DM1.

Evidence of activity of T-DM1 in heavily pretreated patients with metastatic, HER2-overexpressed breast cancer who had received previous trastuzumab and lapatinib was shown in the randomized phase III TH3RESA study (NCT01419197) of T-DM1 versus physician’s choice of treatment.[76][Level of evidence A1] This trial randomly assigned 602 patients in a 2:1 ratio (404 patients assigned to T-DM1 and 198 patients assigned to physician’s choice) and allowed crossover to T-DM1.

At a median follow-up of 7.2 months in the T-DM1 group and 6.5 months in the physician’s-choice group, median PFS was 6.2 months in the T-DM1 group and 3.3 months in the physician’s-choice group (HR, 0.528; 95% CI, 0.422–0.661; P < .0001).

Evidence of activity of T-DM1 in heavily pretreated patients with metastatic, HER2-overexpressed breast cancer who had received previous trastuzumab and lapatinib was shown in the randomized phase III TH3RESA study (NCT01419197) of T-DM1 versus physician’s choice of treatment.[76][Level of evidence A1] This trial randomly assigned 602 patients in a 2:1 ratio (404 patients assigned to T-DM1 and 198 patients assigned to physician’s choice) and allowed crossover to T-DM1.

OS was significantly longer with trastuzumab emtansine versus the treatment of physician’s choice (median OS, 22.7 months vs. 15.8 months; HR, 0.68; 95% CI, 0.54–0.85; P = .0007).[77]

The role of T-DM1 as first-line treatment of metastatic HER2-overexpressed breast cancer was evaluated in the phase III MARIANNE trial (NCT01120184).[78][Level of evidence B1] This study randomly assigned 1,095 patients to receive either trastuzumab plus taxane, T-DM1 plus placebo, or T-DM1 plus pertuzumab.

The role of T-DM1 as first-line treatment of metastatic HER2-overexpressed breast cancer was evaluated in the phase III MARIANNE trial (NCT01120184).[78][Level of evidence B1] This study randomly assigned 1,095 patients to receive either trastuzumab plus taxane, T-DM1 plus placebo, or T-DM1 plus pertuzumab.

The median PFS for these treatment groups was 13.7 months for the trastuzumab-plus-taxane group, 14.1 months for the T-DM1-plus-placebo group, and 15.2 months for the T-DM1-plus-pertuzumab group.

The role of T-DM1 as first-line treatment of metastatic HER2-overexpressed breast cancer was evaluated in the phase III MARIANNE trial (NCT01120184).[78][Level of evidence B1] This study randomly assigned 1,095 patients to receive either trastuzumab plus taxane, T-DM1 plus placebo, or T-DM1 plus pertuzumab.

There was no significant difference in PFS with T-DM1 plus placebo compared with trastuzumab plus taxane (HR, 0.91; 97.5% CI, 0.73–1.13), or with T-DM1 plus pertuzumab compared with trastuzumab plus taxane (HR, 0.87; 97.5% CI, 0.69–1.08).

The role of T-DM1 as first-line treatment of metastatic HER2-overexpressed breast cancer was evaluated in the phase III MARIANNE trial (NCT01120184).[78][Level of evidence B1] This study randomly assigned 1,095 patients to receive either trastuzumab plus taxane, T-DM1 plus placebo, or T-DM1 plus pertuzumab.

Therefore, neither T-DM1 plus placebo nor T-DM1 plus pertuzumab showed PFS superiority over trastuzumab plus taxane.