title: PRONOUNCE: randomized, open-label, phase III study of first-line pemetrexed + carboplatin followed by maintenance pemetrexed versus paclitaxel + carboplatin + bevacizumab followed by maintenance bevacizumab in patients ith advanced nonsquamous non-small-cell lung cancer.
abstract: BACKGROUND
  PRONOUNCE compared the efficacy and safety of pemetrexed+carboplatin followed by pemetrexed (Pem+Cb) with paclitaxel+carboplatin+bevacizumab followed by bevacizumab (Pac+Cb+Bev) in patients with advanced nonsquamous non-small-cell lung cancer (NSCLC).
  
  
  METHODS
  Patients ≥18 years of age with stage IV nonsquamous NSCLC (American Joint Committee on Cancer v7.0), and Eastern Cooperative Oncology Group performance status 0/1 were randomized (1:1) to four cycles of induction Pem+Cb (pemetrexed, 500 mg/m, carboplatin, area under the curve = 6) followed by Pem maintenance or Pac+Cb+Bev (paclitaxel, 200 mg/m, carboplatin, area under the curve = 6, and bevacizumab, 15 mg/kg) followed by Bev maintenance in the absence of progressive disease or discontinuation. The primary objective was progression-free survival (PFS) without grade 4 toxicity (G4PFS). Secondary end points were PFS, overall survival (OS), overall response rate (ORR), disease control rate (DCR), and safety. Resource utilization was also assessed.
  
  
  RESULTS
  Baseline characteristics of the patients randomized to Pem+Cb (N = 182) and Pac+Cb+Bev (N = 179) were well balanced between the arms. Median (months) G4PFS was 3.91 for Pem+Cb and 2.86 for Pac+Cb+Bev (hazard ratio = 0.85, 90% confidence interval, 0.7-1.04; p = 0.176); PFS, OS, ORR, or DCR did not differ significantly between the arms. Significantly more drug-related grade 3/4 anemia (18.7% versus 5.4%) and thrombocytopenia (24.0% versus 9.6%) were reported for Pem+Cb. Significantly more grade 3/4 neutropenia (48.8% versus 24.6%), grade 1/2 alopecia (28.3% versus 8.2%), and grade 1/2 sensory neuropathy were reported for Pac+Cb+Bev. Number of hospitalizations and overall length of stay did not differ significantly between the arms.
  
  
  CONCLUSIONS
  Pem+Cb did not produce significantly better G4PFS compared with Pac+Cb+Bev. Pem+Cb was not superior in PFS, OS, ORR, or DCR compared with Pac+Cb+Bev. Both regimens were well tolerated, although, toxicity profiles differed.
authors.affiliation: *Department of Investigational Cancer therapeutics, University of Texas M. D. Anderson Cancer Center, Houston, Texas; †Global Diversity/Med Affairs, Eli Lilly and Company, Indianapolis, Indiana; ‡Medical Oncology, Tennessee Oncology, Nashville, Tennessee; §Hematology/Oncology, Florida Cancer Specialists, Fort Myers, Florida; •Medical Oncology, Highlands Oncology Group, Fayetteville, Arkansas; ¶Hematology-Medical Oncology, Oncology Heamatology Care Inc., Blue Ash, Ohio; #Hematology & Oncology, Internal Medicine, ACRC/Arizona Clinical Research Center, Arizona Oncology, Tucson, Arizona; **Hematology and Oncology, Michigan State University, East Lansing, Michigan; ††Northeast Georgia Cancer Care, University of Georgia Health Sciences University, Athens, Georgia; ‡‡Statistics Oncology, §§CDK4/6 Product Team, GPORWE-Oncology, ¶¶Oncology-Global Strategic Plan, ##Oncology-Early Phase, ***US Med Affairs and Late Phase Prod Dev, †††Global Medical Communications-Oncology, and ‡‡‡Global Med Affairs & Late Phase Prod Dev, Eli Lilly and Company, Indianapolis, Indiana; §§§Department of Medicine, Oncology Division, Washington University Medical School, St. Louis, Missouri; and ••Hematology/Oncology, Mayo Clinic Arizona, Scottsdale, Arizona.
authors.forename: Ralph G
authors.initials: RG
authors.lastname: Zinner
authors.forename: Coleman K
authors.initials: CK
authors.lastname: Obasaju
authors.forename: David R
authors.initials: DR
authors.lastname: Spigel
authors.forename: Robert W
authors.initials: RW
authors.lastname: Weaver
authors.forename: J Thaddeus
authors.initials: JT
authors.lastname: Beck
authors.forename: David M
authors.initials: DM
authors.lastname: Waterhouse
authors.forename: Manuel R
authors.initials: MR
authors.lastname: Modiano
authors.forename: Borys
authors.initials: B
authors.lastname: Hrinczenko
authors.forename: Petros G
authors.initials: PG
authors.lastname: Nikolinakos
authors.forename: Jingyi
authors.initials: J
authors.lastname: Liu
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Koustenis
authors.forename: Katherine B
authors.initials: KB
authors.lastname: Winfree
authors.forename: Symantha A
authors.initials: SA
authors.lastname: Melemed
authors.forename: Susan C
authors.initials: SC
authors.lastname: Guba
authors.forename: Waldo I
authors.initials: WI
authors.lastname: Ortuzar
authors.forename: Durisala
authors.initials: D
authors.lastname: Desaiah
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Treat
authors.forename: Ramaswamy
authors.initials: R
authors.lastname: Govindan
authors.forename: Helen J
authors.initials: HJ
authors.lastname: Ross
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D000068258:Bevacizumab; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005971:Glutamates / Q000008:administration & dosage; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage; D000068437:Pemetrexed
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D005971:Glutamates; D000068437:Pemetrexed; D000068258:Bevacizumab; D006147:Guanine; D016190:Carboplatin; D017239:Paclitaxel