The combination of capecitabine and trastuzumab has been found to be clinically active in pre-treated patients with HER-2 positive advanced breast cancer.r
The evidence supporting this protocol comes from a Phase III, open-label, randomised, multicentre trial comparing capecitabine with capecitabine plus trastuzumab in patients with HER-2 positive locally advanced or metastatic breast cancer, who had progressed during treatment with trastuzumab.r
Between September 2003 and July 2007, 78 patients were randomly assigned to receive capecitabine (1250 mg/m2 twice a day on days 1-14) and continuation of trastuzumab (6 mg/kg body weight) in 3 week cycles, and 78 patients were randomised to receive capecitabine alone.
The primary end point was time to progression (TTP), with secondary end points of overall response rates (ORR) and overall survival (OS).
Efficacy
After a median follow-up of 15.6 months, the median time to progression was significantly improved in the capecitabine-plus-trastuzumab group (8.2 months) compared to the capecitabine alone group (5.6 months) (HR = 0.69, 95% CI, 0.48-0.97; p = 0.0338). The overall response rates were 27% with capecitabine and 48.1% with capecitabine-plus-trastuzumab, which was a statistically significant improvement (OR, 2.50, p = 0.0115). The median overall survival times were 20.4 months (95% CI, 17.8-24.7) in the capecitabine alone group and 25.5 months (95% CI, 19.0-30.7) in the capecitabine-plus-trastuzumab group (p = 0.257), which was not statistically significant.
Kaplan-Meier estimates of: (A) Progression-free Survival; and (B) Overall Survival
© Journal of Clinical Oncology 2009
Toxicity
There was no significant difference in the number of patients experiencing grade 3 or 4 toxicities between the two groups, with 66.2% of patients in the capecitabine-alone group and 63.6% of patients in the capecitabine-plus-trastuzumab group (p=0.865).
Four patients in the capecitabine-plus-trastuzumab group experienced severe cardiac events (including congestive heart failure, tachyarrhythmia and hypertension). A decrease of LVEF to less than 40% or by greater than 10% from baseline was observed in one patient in the capecitabine-plus-trastuzumab group and was not observed in any of the patients in the capecitabine alone group.r
There were no therapy-related deaths reported.
Grade 3 or 4 adverse eventsr |
Capecitabine alone (%) |
Capecitabine plus trastuzumab (%) |
Neutropenia |
4.4 |
5.33 |
Febrile neutropenia |
0 |
2.6 |
Thrombocytopenia |
1.4 |
0 |
Anemia |
2.8 |
0 |
Vomiting |
4.1 |
1.3 |
Diarrhoea |
18.9 |
15.6 |
Mucositis |
2.7 |
1.3 |
Allergic reaction |
0 |
0 |
Edema |
1.4 |
0 |
Fatigue |
5.4 |
3.9 |
Skin changes (including hand-foot syndrome) |
24.3 |
32.5 |
Nail changes |
0 |
3.9 |
Sensory neuropathy |
5.4 |
2.6 |
Infection |
8.1 |
2.6 |
Fever |
0 |
1.3 |
Dyspnoea |
6.8 |
2.6 |
Cardiovascular disorder* |
2.7 |
5.2 |
*according to NYHA classification