Toxicity
T-DM1 regimen is less toxic than lapatinib and capecitabine. Serious adverse events in the safety population were reported in 18% of the patients in the lapatinib–capecitabine group vs. 15.5% in the T-DM1 group.r
The incidence rates of adverse events of grade 3 or above were higher in the lapatinib–capecitabine group than in the T-DM1 group (57.0% vs. 40.8%). Diarrhoea and palmar–plantar erythrodysesthesia were the most commonly reported grade 3 or 4 events in the lapatinib–capecitabine group, affecting 20.7% and 16.4% of patients, respectively. The most commonly reported grade 3 or 4 events with T-DM1 were thrombocytopenia (12.9%) and elevated serum concentrations of aspartate aminotransferase (AST) (4.3%) and alanine aminotransferase (ALT) (2.9%).r
For most patients, the first occurrence of grade 3 or 4 thrombocytopenia was reported during the first two cycles of T-DM1 treatment; with dose modifications, the majority of these patients were able to continue treatment (10 patients [2.0%] discontinued T-DM1 because of thrombocytopenia).r
The overall incidence of bleeding events was higher with T-DM1 (29.8%, vs. 15.8% with lapatinib plus capecitabine); rates of grade 3 or 4 bleeding events were low in both groups (1.4% and 0.8%, respectively).r
In the majority of patients, a left ventricular ejection fraction of 45% or more was maintained during the study treatment (in 97.1% of patients in the T-DM1 group and 93.0% of patients in the lapatinib–capecitabine group). Three patients in each group had a decrease from baseline to less than 40%. 1.7% of patients in the T-DM1 group and 1.6% of patients in the lapatinib–capecitabine group had an ejection fraction that was less than 50% and at least 15 percentage points below the baseline value.r
96.1% and 96.8% of deaths occurring during the study period were attributed to disease progression in the lapatinib–capecitabine group and T-DM1 group respectively. Five deaths were attributed to adverse events that occurred within 30 days after the last dose of a study drug: 4 deaths in the lapatinib–capecitabine group (due to coronary artery disease, multi-organ failure, coma, and hydrocephalus) and 1 death in the T-DM1 group (due to metabolic encephalopathy after CNS progression).r
Adverse eventsr
© New England Journal of Medicine 2012