title: Bavituximab plus paclitaxel and carboplatin for the treatment of advanced non-small-cell lung cancer.
abstract: OBJECTIVE
  Bavituximab is a phosphatidylserine (PS)-targeting monoclonal antibody with immune-modulating and tumor-specific vascular targeting properties. Preclinical studies have shown activity against numerous solid tumors and at least an additive effect in combination with chemotherapy. This study evaluated bavituximab in combination with paclitaxel and carboplatin in patients with previously untreated, locally advanced or metastatic non-small-cell lung cancer (NSCLC).
  
  
  METHODS
  This phase II, open-label study (NCT00687817) was conducted in 49 patients with stage IIIB/IV NSCLC utilizing a Simon two-stage design. Patients were treated with up to six cycles of carboplatin area under the concentration-time curve (AUC) 5 plus paclitaxel 175 mg/m2 every 21 days with weekly bavituximab 3 mg/kg followed by bavituximab monotherapy until progression or unacceptable toxicity.
  
  
  RESULTS
  The primary efficacy endpoint of overall response rate (ORR) was 40.8% (complete response [CR] 2.0%, partial response [PR] was 38.8%). Median progression-free survival (PFS) and overall survival (OS) were 6.0 and 12.4 months, respectively. Treatment-related adverse events (AEs) occurred in 40.8% of patients. The most common treatment-related AEs were anemia (10.2%), asthenia, vomiting, paresthesia, anorexia, and fatigue (6.1% each). One patient with a central, cavitating squamous tumor developed fatal hemoptysis and aspiration.
  
  
  CONCLUSIONS
  Bavituximab in combination with paclitaxel-carboplatin as first-line therapy demonstrated a tolerable safety profile and potential efficacy in this single-arm phase II trial in patients with advanced local or metastatic NSCLC. Randomized trials with this regimen are in progress.
  
  
  BACKGROUND
  NCT00687817.
authors.affiliation: Nizam's Institute of Medical Sciences, Hyderabad, India.
authors.forename: Raghunadharao
authors.initials: R
authors.lastname: Digumarti
authors.affiliation: Apollo Hospitals, Bangalore, India.
authors.forename: P P
authors.initials: PP
authors.lastname: Bapsy
authors.affiliation: Yashoda Hospital, Hyderabad, India.
authors.forename: Attili V
authors.initials: AV
authors.lastname: Suresh
authors.affiliation: Orchid Nursing Home, Kolkata, India.
authors.forename: G S
authors.initials: GS
authors.lastname: Bhattacharyya
authors.affiliation: Kidwai Memorial Institute of Oncology, Bangalore, India.
authors.forename: Lokanatha
authors.initials: L
authors.lastname: Dasappa
authors.affiliation: Peregrine Pharmaceuticals, Inc., Tustin, CA, United States. Electronic address: JShan@peregrineinc.com.
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Shan
authors.affiliation: UT Southwestern Medical Center, Dallas, TX, United States.
authors.forename: David E
authors.initials: DE
authors.lastname: Gerber
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D016190:Carboplatin; D017239:Paclitaxel; C547825:bavituximab
keywords: Bavituximab; Carboplatin; Immune modulation; Monoclonal antibody; Non-small-cell lung cancer; Paclitaxel; Phosphatidylserine