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

Clin Breast Cancer. 2016 Oct;16(5):349-355. doi: 10.1016/j.clbc.2016.05.006. Epub 2016 May 14.

Abstract

Background: 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.

Patients and methods: 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.

Results: 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%).

Conclusion: 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.

Keywords: Chemotherapy; EGFR inhibitor; Metastatic breast cancer; Panitumumab; Triple-negative breast cancer.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Administration, Intravenous
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / therapeutic use
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carboplatin / administration & dosage
  • Carboplatin / adverse effects
  • Carboplatin / therapeutic use
  • Class I Phosphatidylinositol 3-Kinases
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / adverse effects
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / therapeutic use
  • Disease-Free Survival
  • ErbB Receptors / antagonists & inhibitors*
  • ErbB Receptors / metabolism
  • Female
  • Gemcitabine
  • Humans
  • Middle Aged
  • Neoplasm Staging
  • PTEN Phosphohydrolase / metabolism
  • Panitumumab
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins p21(ras) / metabolism
  • Signal Transduction / drug effects
  • Treatment Outcome
  • Triple Negative Breast Neoplasms / drug therapy*
  • Triple Negative Breast Neoplasms / metabolism
  • Triple Negative Breast Neoplasms / mortality*
  • Triple Negative Breast Neoplasms / pathology
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • KRAS protein, human
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Deoxycytidine
  • Panitumumab
  • Carboplatin
  • Phosphatidylinositol 3-Kinases
  • Class I Phosphatidylinositol 3-Kinases
  • PIK3CA protein, human
  • EGFR protein, human
  • ErbB Receptors
  • PTEN Phosphohydrolase
  • PTEN protein, human
  • Proto-Oncogene Proteins p21(ras)
  • Gemcitabine