medwireNews: The addition of capecitabine to trastuzumab emtansine (T-DM1) does not improve the clinical outcomes of patients with previously treated HER2-positive metastatic breast cancer, indicates the phase 1/2 TRAXHER2 study.
The investigators also note that the incidence of adverse events (AEs) was higher in the combination than T-DM1 alone group, although “no unexpected toxic effects” were observed.
In the phase 2 trial, 81 patients who had received at least one prior line of therapy were randomly assigned to receive the maximum tolerated dose – as determined in the phase 1 trial – of capecitabine 700 mg/m2 twice daily for the first 14 days of each 3-week cycle plus T-DM1 3.6 mg/kg every 3 weeks, while the remaining 80 patients received T-DM1 alone.
As reported in JAMA Oncology, there was no significant difference in the overall response rate between those who received the combination and those who received T-DM1 alone, at 44.4% and 36.3%, respectively. The corresponding clinical benefit rates were also comparable, at 66.7% and 62.5%.
Median progression-free survival was 10.2 months and median overall survival was not estimable in the combination group, with corresponding durations in the T-DM1 alone group of 9.8 and 24.7 months.
In the combination arm, 33% of patients required a dose reduction and 54% required a dose delay of T-DM1 versus comparable corresponding rates of 37% and 56% in the T-DM1 alone arm. However, the rate of study or treatment discontinuation due to adverse events (AEs) was higher in the combination than the T-DM1 monotherapy group, at 28% versus 15%.
Grade 3–4 AEs were reported in 44% of patients receiving capecitabine plus T-DM1 and 41% of those given T-DM1 alone, most commonly thrombocytopenia (10 vs 4%), increased aspartate aminotransferase (5 vs 6%), and increased gamma-glutamyltransferase (5 vs 6%).
Although the addition of capecitabine to T-DM1 did not lead to improved efficacy in this study, Karen Gelmon (University of British Colombia, Vancouver, Canada) and colleagues suggest that “it is possible that different dose combinations or schedules may improve outcomes.”
They continue: “Further studies may provide additional data, including a phase 1 study of T-DM1 plus nonpegylated liposomal doxorubicin (MEDOPP038; THELMA).
“Other studies are investigating targeted therapy combinations, including T-DM1 plus tyrosine kinase inhibitors.”
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