| PurposeTo compare efficacy and safety of vinorelbine or capecitabine, both with trastuzumab for HER2-positive metastatic breast cancer patients who have previously received taxanes. To explore the study on correlation between the efficacy and p53.MethodsAll patients were HER2 positive metastatic breast cancer with heavily pretreated. They were assigned to vinorelbine(N) 25 mg/m2 on days 1 and 8 or capecitabine(X) 2000 mg/m2 day 1 to day 14, both combined with trastuzumab(H) 8-mg/kg loading dose and 6-mg/kg maintenance dose on day 1 every 3 weeks. The main endpoint was PFS. Second endpoints were OS, ORR, CBR and hematologic adverse events. According to the hormone receptor status, compare efficacy of hormone receptor positive and hormone receptor negative HER2-positive metastatic breast cancer patients. P53 mutational analysis using the immunohistochemical (IHC) and ≥10% tumor cells staining was considered positive.Results1. Among 163 assigned patients, the median PFS for vinorelbine plus trastuzumab (NH) and capecitabine plus trastuzumab (XH) was 4.9 vs.6.5 months, respectively(P=0.005), median OS was 28.6 vs 34.4 months (P=0.115). However the objective response rate(ORR:45.7% vs 26.8%, P=0.012) was higher with vinorelbine group. Clinical benefit rate(CBR:54.3% vs 58.5%, P=0.820) no statistical difference was observed. Grade 3 to 4 hematologic toxicity was more common in the vinorelbine group compared with the capecitabine group, especially with rates of neutropenia of 58% versus 19% (P<0.001), leucopenia of 56% versus 12%(P<0.001). In subgroup analysis, the patients received vinorelbine plus trastuzumab who had visceral metastasis, multiple metastases, heavily pretreated or received non-trastuzumab before obtained better ORR. However, the patients received capecitabine plus trastuzumab who HR negative, heavily pretreated or received trastuzumab before obtained longer PFS and heavily pretreated still obtained longer OS(26.5 vs 28.5 months, p=0.016).2. HR positive were 91 patients and HR negative 72. PFS(5.1 vs 5.6 months, p=0.167), OS(28.6 vs 30.9 months, p=0.269), ORR(30.8% vs 41.7%, p=0.149) and CBR(54.3% vs 58.5%, p=0.820) no statistical difference were observed respectively. In capecitabine group, HR negative patients obtained better ORR(36.8% vs 15.9%, p=0.149) and in visceral metastasis or HR positive patients obtained longer PFS (5.5 vs 4.6 months, p=0.033).3. P53 protein expression were tested in 47 patients. Positive expression rate was 42.6%. Objective response rate was 50.0% and 22.2% of p53 positive and negative respectively, p=0.047. No statistical difference were observed in median PFS (7.0 vs 6.2 months, p=0.851), median OS (35.6 vs 37.7 months, p=0.909), CBR(60.0% vs 55.6%, p=0.761). In p53 negative patients, capecitabine group obtained longer PFS (11.0 vs 3.2 months, p=0.027).Conclusions1. For HER2-positive metastatic breast cancer previously treated with taxanes, when patients with disease progression rapidly and well general condition, especially with visceral metastases or multiple metastases, in order to rapid control of the disease recurrence should be given vinorelbine plus trastuzumab. When patients with disease progression slowly and poor general condition, especially with HR negative or previously treated with trastuzumab, should be given capecitabine plus trastuzumab to prolong PFS and enhance the quality of life.2. HR status was not significantly correlation with efficacy of anti-HER2. HR negative with visceral metastases patients should be given chemotherapy combine with anti-HER2 drug as soon as possible.3. There was difference between ORR to positive rates of p53 expression. P53 maybe is one of predictive factors about efficacy of capecitabine. |
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