Two RCTs and 10 uncontrolled studies were included: 1 RCT (111 participants) and 2 uncontrolled studies (256 participants) evaluated trastuzumab as a single agent, while 1 RCT (469 participants) and 8 uncontrolled studies (237 participants) evaluated it in combination with chemotherapy.
Single-agent trastuzumab.
One RCT (111 patients evaluated) comparing a standard dose and high dose of trastuzumab in women who had not previously received chemotherapy reported similar outcomes with both regimens. The overall response rate was 26.1% (95% confidence interval, CI: 18.0, 34.3) with a median duration of survival of 24.4 months. In 2 uncontrolled studies of 43 and 213 patients who had received prior chemotherapy, the respective overall response rates were 11.6% (95% CI: 4.5, 26), with a median time to progression of 5.1 months, and 14.6% (95% CI: 11, 21), with a response duration of 9.1 months.
Trastuzumab in combination with chemotherapy.
One RCT (469 patients evaluated) reported a statistically significant improvement in overall response rate (50% versus 32%, P<0.001), time to treatment failure (6.9 versus 4.5 months, P<0.001), response duration (9.1 versus 6.1 months, P<0.001), time to progression and overall survival (median 25.1 months versus 20.3 months, P=0.046) with trastuzumab plus chemotherapy compared with chemotherapy alone. In 8 uncontrolled studies of between 6 and 18 patients, the overall response ranged from 24 to 83%.
Adverse events.
One RCT reported two deaths possibly related to trastuzumab. This trial also reported a higher rate of anaemia (27% versus 19%) and leukopenia (41% versus 26%) when trastuzumab was added to chemotherapy compared with chemotherapy alone. This trial also reported a higher rate of symptomatic or asymptomatic cardiac dysfunction (27% versus 8%) and a higher incidence of grade 3 or 4 New York Heart Association heart failure (16% versus 3%) with trastuzumab. Data from 5 uncontrolled studies indicated a low incidence of cardiac toxicity with trastuzumab plus chemotherapy.