title: NCCTG N0821 (Alliance): a phase II first-line study of pemetrexed, carboplatin, and bevacizumab in elderly patients with advanced nonsquamous non-small-cell lung cancer with good performance status.
abstract: BACKGROUND
  We hypothesized that the combination of bevacizumab, carboplatin, and pemetrexed will be an effective first-line regimen in fit, elderly patients with nonsquamous non-small-cell lung cancer.
  
  
  METHODS
  Treatment-naïve, stage IIIB/IV nonsquamous non-small-cell lung cancer patients more than 70 years old with good performance status (Eastern Cooperative Oncology Group performance status 0-1) and adequate organ function were eligible. Carboplatin area under the curve 6, pemetrexed 500 mg/m, and bevacizumab 15 mg/kg were administered on day 1 of each 21-day cycle (up to six cycles) followed by maintenance pemetrexed and bevacizumab. The primary end point of 6-month progression-free survival rate of at least 70% was assessed using a one-stage binomial design. Quality of life (QOL) questionnaires were administered. Polymorphisms in genes encoding relevant proteins (drug targets, transport, and metabolism proteins) were correlated with treatment outcome.
  
  
  RESULTS
  Fifty-seven eligible patients were enrolled. Median age was 74.5 years. Median treatment cycles received was 6. The most common grade 3 or higher non-hematologic adverse events were fatigue (26%) and hypertension (11%); 16% had grade 4 neutropenia and 6.5% had grade 4 thrombocytopenia. Three patients experienced grade 3/4 hemorrhagic events (one pulmonary, two gastrointestinal). Primary end point of PFS6 was 60% (95% confidence interval [CI]: 45.9-73%). Median PFS was 7.0 months (95% CI: 5.9-10.1), median overall survival was 13.7 months (95% CI: 9.4-16.8). Polymorphic KDR and VEGFA variants correlated with survival and toxicity, respectively. There was no significant change in overall QOL scores over time.
  
  
  CONCLUSIONS
  This regimen is feasible and did not decrease the QOL in this study population. However, it did not meet the primary efficacy end point.
authors.affiliation: *Roswell Park Cancer Institute, Buffalo, NY; †Mayo Clinic Rochester, MN 55905; ‡Michiana Hematology Oncology, South Bend, IN; §Illinois CancerCare, Ottawa, IL; ‖Mayo Clinic Scottsdale, AZ; ¶Missouri Valley Cancer Consortium, Omaha, NE; and #Metro-Minnesota Community Clinical Oncology Program, St. Louis Park, MN.
authors.forename: Grace K
authors.initials: GK
authors.lastname: Dy
authors.forename: Julian R
authors.initials: JR
authors.lastname: Molina
authors.forename: Yingwei
authors.initials: Y
authors.lastname: Qi
authors.forename: Rafat
authors.initials: R
authors.lastname: Ansari
authors.forename: Sachdev
authors.initials: S
authors.lastname: Thomas
authors.forename: Helen J
authors.initials: HJ
authors.lastname: Ross
authors.forename: Gamini
authors.initials: G
authors.lastname: Soori
authors.forename: Daniel
authors.initials: D
authors.lastname: Anderson
authors.forename: Marie Christine
authors.initials: MC
authors.lastname: Aubry
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Meyers
authors.forename: Araba A
authors.initials: AA
authors.lastname: Adjei
authors.forename: Sumithra
authors.initials: S
authors.lastname: Mandrekar
authors.forename: Alex A
authors.initials: AA
authors.lastname: Adjei
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D018572:Disease-Free Survival; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D005838:Genotype; D005971:Glutamates / Q000008:administration & dosage; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D006973:Hypertension / Q000139:chemically induced; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D008297:Male; D009503:Neutropenia / Q000139:chemically induced; D062072:Patient Acuity; D000068437:Pemetrexed; D020641:Polymorphism, Single Nucleotide; D011788:Quality of Life; D058978:Reduced Folate Carrier Protein / Q000235:genetics; D015996:Survival Rate; D013921:Thrombocytopenia / Q000139:chemically induced; D013940:Thymidylate Synthase / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D005971:Glutamates; D058978:Reduced Folate Carrier Protein; C548699:SLC19A1 protein, human; D042461:Vascular Endothelial Growth Factor A; D000068437:Pemetrexed; D000068258:Bevacizumab; D006147:Guanine; D016190:Carboplatin; D013940:Thymidylate Synthase; D040301:Vascular Endothelial Growth Factor Receptor-2