title: Panitumumab, Gemcitabine, and Carboplatin as Treatment for Women With Metastatic Triple-Negative Breast Cancer: A Sarah Cannon Research Institute Phase II Trial.
abstract: 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.
authors.affiliation: Sarah Cannon Research Institute, Nashville, TN; Tennessee Oncology, PLLC, Nashville, TN. Electronic address: dyardley@tnonc.com.
authors.forename: Denise A
authors.initials: DA
authors.lastname: Yardley
authors.affiliation: Sarah Cannon Research Institute, Nashville, TN; Oncology Hematology Care, Cincinnati, OH.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Ward
authors.affiliation: Sarah Cannon Research Institute, Nashville, TN; Tennessee Oncology Chattanooga, Chattanooga, TN.
authors.forename: Brooke R
authors.initials: BR
authors.lastname: Daniel
authors.affiliation: Sarah Cannon Research Institute, Nashville, TN; Florida Cancer Specialists, Fort Myers, FL.
authors.forename: Janice F
authors.initials: JF
authors.lastname: Eakle
authors.affiliation: Sarah Cannon Research Institute, Nashville, TN; Tennessee Oncology, PLLC, Nashville, TN.
authors.forename: Ruth E
authors.initials: RE
authors.lastname: Lamar
authors.affiliation: Sarah Cannon Research Institute, Nashville, TN.
authors.forename: Cassie M
authors.initials: CM
authors.lastname: Lane
authors.affiliation: Sarah Cannon Research Institute, Nashville, TN; Tennessee Oncology, PLLC, Nashville, TN.
authors.forename: John D
authors.initials: JD
authors.lastname: Hainsworth
mesh_terms: D061605:Administration, Intravenous; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D058534:Class I Phosphatidylinositol 3-Kinases; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005260:Female; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D000077544:Panitumumab; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D016896:Treatment Outcome; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D000093542:Gemcitabine
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; C117307:KRAS protein, human; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D003841:Deoxycytidine; D000077544:Panitumumab; D016190:Carboplatin; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; C512478:EGFR protein, human; D066246:ErbB Receptors; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D016283:Proto-Oncogene Proteins p21(ras); D000093542:Gemcitabine
keywords: Chemotherapy; EGFR inhibitor; Metastatic breast cancer; Panitumumab; Triple-negative breast cancer