A phase II trial of biweekly vinorelbine and oxaliplatin in second- or third-line metastatic triple-negative breast cancer

Abstract

Patients with metastatic triple-negative breast cancer (mTNBC) typically have a poor prognosis. The purpose of this study was to prospectively evaluate the efficacy and toxicity of biweekly combination of vinorelbine and oxaliplatin (NVBOX) in second- or third-line setting for mTNBC. Eligible patients were female with 18-70 y old, and had mTNBC that had progressed after 1or 2 prior chemotherapy regimens in the metastatic setting. NVBOX was given biweekly every 4 week for a maximum of 6 cycles. The primary endpoint was progression-free survival (PFS). Forty-4 patients were recruited. All patients had been exposed to anthracyclines and/or taxanes; 56.8% of patients were cis/carbo-platin pretreated. Among the 38 evaluable patients, overall response rate was 31.6% and 7 lasted ≥ 6 months. The median PFS and overall survival (OS) were 4.3 (95% CI, 3.6-5.0) months and 12.6 (95% CI, 8.1-17.0) months, respectively. PFS and OS was significantly shorter in patients with interval from diagnosis to recurrence ≤ 1 y and time to progression (TTP) of 1-2 previous regimens before recruitment ≤ 3 months. For 34 patients who were treated in second line setting, prior platinum was a factor significantly compromising the PFS of NVBOX. Grade 3/4 hematologic toxicities included neutropenia (70.5%), thrombocytopenia (27.3%) and anemia (15.9%). The most frequent grade 3/4 non-hematologic toxicities were constipation/abdominal distension (20.5%) and nausea/vomiting (13.6%). We conclude that biweekly NVBOX regimen is effective with a good safety profile in the second- or third-line mTNBC, which warrants further investigation in a phase III study. This trial was registered with www.clinicaltrials.gov (no. NCT01528826).

Keywords: AE, adverse events; ANC, absolute neutrophil count; CBR, rate of clinical benefit; CI, confidence interval; CR, complete response; ECOG, Eastern Cooperative Oncology Group; ER, estrogen receptor; FISH, fluorescence in situ hybridization; HER2, human epidermal growth factor receptor 2; HR, hazard ratio; IHC, immunohistochemistry; IV, intravenously; MBC, metastatic breast cancer; ORR, overall response rate; PR, partial response; PgR, progesterone receptor; SD, stable disease; TNBC, triple-negative breast cancer; TTP, time to progression; ULN, upper limit of normal; chemotherapy; mTNBC, metastatic triple-negative breast cancer; metastatic breast cancer; oxaliplatin; triple-negative; vinorelbine.

Figures

Figure 1.

Kaplan-Meier estimates of progression-free survival (PFS) (A) and overall survival (OS) (B) for the ITT population. Kaplan-Meier estimates of PFS (C) and OS (D) for different interval from diagnosis of breast cancer to recurrence (≤ 1 y vs. > 1 year).Kaplan-Meier estimates of PFS (C) and OS (D) for different TTP of 1–2 previous regimens before recruitment (≤ 3 months vs. > 3 months).