A phase II clinical trial of weekly paclitaxel and carboplatin in combination with panitumumab in metastatic triple negative breast cancer

Abstract

Purpose: Women with metastatic triple negative breast cancer (TNBC) can have a poor prognosis with treatment limited to cytotoxic chemotherapy. The identification of effective therapies that may limit exposure to cytotoxic chemotherapy and lead to prolonged survival is an unmet medical need. We tested an inhibitor of the epidermal growth factor receptor, panitumumab in combination with chemotherapy.

Methods: We conducted a single arm clinical trial in women with metastatic or locally advanced TNBC to paclitaxel 80 mg/m2 and carboplatin AUC of 2 on days 1, 8, and 15 and panitumumab 6 mg/kg on days 1 and 15 for a cycle length of 28 days. The objectives were to evaluate the response rate and safety of the combination in comparison to historical controls.

Results: Fourteen patients with TNBC were enrolled with a median age of 53 years. The majority of women were African American (64.3%) with visceral metastasis (64.2%). Hematologic toxicities, particularly neutropenia and thrombocytopenia, were a major cause of missed chemotherapy and delayed treatment in this study. The overall response rate (complete and partial response) of the 13 evaluable patients was 46%. The median time to best response was 2.4 months and the median time to disease progression was 3.6 months. We were able to perform the PAM50 analysis on tumors from 7 of our subjects. All the samples tested clustered within the basal-like subtype.

Conclusions: In our experience the response rate of carboplatin, paclitaxel and panitumumab was consistent with other reports of response for cytotoxic chemotherapy in metastatic TNBC.

Keywords: AUC, area under the curve; CR, complete response; EGFR, Epidermal growth factor inhibitor; FISH, Fluorescence in situ hybridization; Hgb, hemoglobin; IHC, immunohistochemistry; IRB, Institutional Review Board; Mg/dl, milligram/deciliter; Mg/kg, milligram/kilogram; PD, progressive disease; PR, partial response; RECIST, response evaluation in sold tumors; TNBC, triple negative breast cancer; epidermal growth factor inhibitor; g/dl, grams/deciliter; metastatic breast cancer; pacliataxel carboplatin; triple negative breast cancer.

Figure 1.

PAM 50 on 7 subjects prior to treatment.