title: Results of a Phase II Trial of Carboplatin, Pemetrexed, and Bevacizumab for the Treatment of Never or Former/Light Smoking Patients With Stage IV Non-Small Cell Lung Cancer.
abstract: BACKGROUND
  Bevacizumab- and pemetrexed-based therapies have demonstrated activity in patients with non-small-cell lung cancer (NSCLC) and nonsquamous histologic features. Patients with history of never or light smoking might derive greater benefit from these therapies.
  
  
  METHODS
  The included patients had stage IIIB (malignant pleural effusion) or IV NSCLC with nonsquamous histologic features, adequate organ function, no contraindications to bevacizumab, and no previous cytotoxic therapy. The patients had also never smoked or had smoked ≤ 10 pack years and had quit ≥ 1 year before enrollment. The patients had received 4 cycles of carboplatin (area under the curve, 6), pemetrexed 500 mg/m(2), and bevacizumab 15 mg/kg. Patients without disease progression initiated maintenance therapy with pemetrexed and bevacizumab. A single-arm phase II trial with the primary endpoint of progression-free survival (PFS) was performed. The secondary endpoints were the objective response rate (ORR), overall survival (OS), and toxicity.
  
  
  RESULTS
  From March 2010 to November 2013, 38 eligible patients were enrolled and treated in the trial. The most common histologic type was adenocarcinoma (97%). Most of the patients were women (66%) and never smokers (63%). The median PFS was 12.6 months (95% confidence interval [CI], 8.0-23.9 months). The ORR and OS were 47% (95% CI, 31%-64%) and 20.3 months (95% CI, 15.8-30.5 months). The grade 3 or 4 toxicities occurring at rate of ≥ 10% were neutropenia (18%), anemia (16%), fatigue (16%), hypertension (16%), and thrombocytopenia (11%).
  
  
  CONCLUSIONS
  The combination of the carboplatin, pemetrexed, and bevacizumab demonstrated activity with acceptable toxicity in patients with a clinical history of never or light smoking.
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC. Electronic address: Jared_Weiss@med.unc.edu.
authors.forename: Jared M
authors.initials: JM
authors.lastname: Weiss
authors.affiliation: University of Pittsburgh Medical Center, Pittsburgh, PA.
authors.forename: Liza C
authors.initials: LC
authors.lastname: Villaruz
authors.affiliation: Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC.
authors.forename: Jonathon
authors.initials: J
authors.lastname: O'Brien
authors.affiliation: Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Ivanova
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC.
authors.forename: Carrie
authors.initials: C
authors.lastname: Lee
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC.
authors.forename: Juneko Grilley
authors.initials: JG
authors.lastname: Olson
authors.affiliation: Cancer Care of Western North Carolina, Asheville, NC.
authors.forename: Gregory
authors.initials: G
authors.lastname: Pollack
authors.affiliation: New Bern Cancer Center, New Bern, NC.
authors.forename: Richard
authors.initials: R
authors.lastname: Gorman
authors.affiliation: University of Pittsburgh Medical Center, Pittsburgh, PA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Socinski
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Stinchombe
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000209:etiology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000008:administration & dosage / Q000009:adverse effects; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009503:Neutropenia / Q000209:etiology; D000068437:Pemetrexed / Q000008:administration & dosage / Q000009:adverse effects; D012907:Smoking; D016019:Survival Analysis; D016896:Treatment Outcome; D014481:United States
chemical_list: D000068437:Pemetrexed; D000068258:Bevacizumab; D016190:Carboplatin
keywords: Adenocarcinoma; Bevacizumab; Carboplatin; Light smoker; Never smoker; Pemetrexed