Lani
03-03-2007, 07:14 PM
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With comparable efficacy results for the trastuzumab containing arms, the toxicity profiles become more important because the benefit provided by trastuzumab is always associated with some risk. When considering the therapeutic index of the 2 trastuzumab-containing arms, the small, nonstatistically significant difference between TCH and AC-TH needs to be considered in light of the differences in the adverse effects when selecting adjuvant therapy. The cardiac toxicity of the 2 experimental arms significantly favored the TCH regimen. However, no cardiac deaths were observed in either arm. There were 20 congestive heart failure events in the AC-TH arm compared with 4 events in the TCH arm. Moreover, there were 50% fewer asymptomatic declines in left ventricular ejection fraction in the TCH arm compared with the AC-TH arm. Even when considering noncardiac toxicity, the TCH arm appeared to be superior to AC-TH. In particular, the rate of sensory neuropathy was 36.1% for patients who received TCH vs 49.7% for patients given AC-TH. Likewise, nail changes were reported in 28.7% of those in the TCH cohort vs 43.6% in the AC-TH arm. Fewer myalgias (38.6% vs 55.5%) were observed in the TCH vs AC-TH groups. However, more grade 3 and 4 thrombocytopenia (5.4% vs 1.2%) and anemia (5.8% vs 3.1%) were observed in the TCH arm compared with the AC-TH arm. It is also important to note that 4 patients in the anthracycline- and cyclophosphamide-containing arms developed leukemia, whereas no leukemias occurred in the TCH arm.
In considering the therapeutic index for the 2 trastuzumab-containing arms, it seems prudent to weigh the nonstatistically significant benefit for AC-TH (a decrease of 14 DFS events) against the increase in cardiac toxicity, leukemia incidence, and overall safety profile.
With comparable efficacy results for the trastuzumab containing arms, the toxicity profiles become more important because the benefit provided by trastuzumab is always associated with some risk. When considering the therapeutic index of the 2 trastuzumab-containing arms, the small, nonstatistically significant difference between TCH and AC-TH needs to be considered in light of the differences in the adverse effects when selecting adjuvant therapy. The cardiac toxicity of the 2 experimental arms significantly favored the TCH regimen. However, no cardiac deaths were observed in either arm. There were 20 congestive heart failure events in the AC-TH arm compared with 4 events in the TCH arm. Moreover, there were 50% fewer asymptomatic declines in left ventricular ejection fraction in the TCH arm compared with the AC-TH arm. Even when considering noncardiac toxicity, the TCH arm appeared to be superior to AC-TH. In particular, the rate of sensory neuropathy was 36.1% for patients who received TCH vs 49.7% for patients given AC-TH. Likewise, nail changes were reported in 28.7% of those in the TCH cohort vs 43.6% in the AC-TH arm. Fewer myalgias (38.6% vs 55.5%) were observed in the TCH vs AC-TH groups. However, more grade 3 and 4 thrombocytopenia (5.4% vs 1.2%) and anemia (5.8% vs 3.1%) were observed in the TCH arm compared with the AC-TH arm. It is also important to note that 4 patients in the anthracycline- and cyclophosphamide-containing arms developed leukemia, whereas no leukemias occurred in the TCH arm.
In considering the therapeutic index for the 2 trastuzumab-containing arms, it seems prudent to weigh the nonstatistically significant benefit for AC-TH (a decrease of 14 DFS events) against the increase in cardiac toxicity, leukemia incidence, and overall safety profile.