Panitumumab, Gemcitabine, and Carboplatin as Treatment for Women With Metastatic Triple-Negative Breast Cancer: A Sarah Cannon Research Institute Phase II Trial

In this phase II trial we evaluated efficacy and safety of panitumumab in combination with gemcitabine and carboplatin as treatment for metastatic triple-negative breast cancer (TNBC). Seventy-one women were treated. The median progression-free survival was 4.4 months. The results of this trial do not support combination of panitumumab with gemcitabine and carboplatin in the treatment of patients with TNBC. Triple-negative breast cancer (TNBC) is a subtype with poor prognosis, and treatment options are limited to chemotherapy. Because the epidermal growth factor receptor (EGFR) is overexpressed in up to 70% of these tumors, this phase II trial was designed to evaluate the efficacy and safety of panitumumab in combination with gemcitabine and carboplatin as first- or second-line treatment for metastatic TNBC. Adult women with metastatic TNBC with a maximum of 1 previous chemotherapy regimen were eligible. Patients received gemcitabine intravenous (I.V.) 1500 mg/m2, carboplatin area under the concentration-time curve = 2.5 I.V., and panitumumab 6 mg/kg I.V. every 2 weeks. Treatment continued until disease progression or unacceptable toxicity, with disease evaluations every 6 weeks. The primary end point was progression-free survival (PFS). Archival tissue was collected for correlative analysis, to include phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha, p53, phosphatase and tensin homolog, EGFR, and status. Between May 2010 and August 2012, 71 women (median age, 54 years; 14% de novo stage IV) were treated. At a median follow-up of 11 months, the median PFS was 4.4 months (95% confidence interval, 3.2-5.5 months). The objective response rate was 42% (complete response, 1; partial response, 29). Treatment-related toxicity included: rash, 50 patients (70%), fatigue, 37 patients (52%), neutropenia, 32 patients (45%; 2 episodes of febrile neutropenia), and thrombocytopenia, 32 patients (45%). Although the addition of panitumumab was feasible, the results of this trial do not support combination of panitumumab with gemcitabine and carboplatin in the treatment of patients with TNBC.