title: PointBreak: a randomized phase III study of pemetrexed plus carboplatin and bevacizumab followed by maintenance pemetrexed and bevacizumab versus paclitaxel plus carboplatin and bevacizumab followed by maintenance bevacizumab in patients with stage IIIB or IV nonsquamous non-small-cell lung cancer.
abstract: OBJECTIVE
  PointBreak (A Study of Pemetrexed, Carboplatin and Bevacizumab in Patients With Nonsquamous Non-Small Cell Lung Cancer) compared the efficacy and safety of pemetrexed (Pem) plus carboplatin (C) plus bevacizumab (Bev) followed by pemetrexed plus bevacizumab (PemCBev) with paclitaxel (Pac) plus carboplatin (C) plus bevacizumab (Bev) followed by bevacizumab (PacCBev) in patients with advanced nonsquamous non-small-cell lung cancer (NSCLC).
  
  
  METHODS
  Patients with previously untreated stage IIIB or IV nonsquamous NSCLC and Eastern Cooperative Oncology Group performance status of 0 to 1 were randomly assigned to receive pemetrexed 500 mg/m(2) or paclitaxel 200 mg/m(2) combined with carboplatin area under the curve 6 and bevacizumab 15 mg/kg every 3 weeks for up to four cycles. Eligible patients received maintenance until disease progression: pemetrexed plus bevacizumab (for the PemCBev group) or bevacizumab (for the PacCBev group). The primary end point of this superiority study was overall survival (OS).
  
  
  RESULTS
  Patients were randomly assigned to PemCBev (n = 472) or PacCBev (n = 467). For PemCBev versus PacCBev, OS hazard ratio (HR) was 1.00 (median OS, 12.6 v 13.4 months; P = .949); progression-free survival (PFS) HR was 0.83 (median PFS, 6.0 v 5.6 months; P = .012); overall response rate was 34.1% versus 33.0%; and disease control rate was 65.9% versus 69.8%. Significantly more study drug-related grade 3 or 4 anemia (14.5% v 2.7%), thrombocytopenia (23.3% v 5.6%), and fatigue (10.9% v 5.0%) occurred with PemCBev; significantly more grade 3 or 4 neutropenia (40.6% v 25.8%), febrile neutropenia (4.1% v 1.4%), sensory neuropathy (4.1% v 0%), and alopecia (grade 1 or 2; 36.8% v 6.6%) occurred with PacCBev.
  
  
  CONCLUSIONS
  OS did not improve with the PemCBev regimen compared with the PacCBev regimen, although PFS was significantly improved with PemCBev. Toxicity profiles differed; both regimens demonstrated tolerability.
authors.affiliation: Jyoti D. Patel, Northwestern University; Philip Bonomi, Rush University Medical Center, Chicago, IL; Mark A. Socinski, University of Pittsburgh, Pittsburgh, PA; Edward B. Garon, University of California at Los Angeles, Los Angeles, CA; Craig H. Reynolds, US Oncology Research, Ocala, FL; David R. Spigel, Sarah Cannon Research Institute-Tennessee Oncology, Nashville, TN; Mark R. Olsen, Tulsa Cancer Institute, Tulsa, OK; Robert C. Hermann, Northwest Georgia Oncology Centers, Marietta, GA; Robert M. Jotte, Rocky Mountain Cancer Centers, Denver, CO; Thaddeus Beck, Highlands Oncology Group, Fayetteville, AR; Donald A. Richards, US Oncology Research, Tyler, TX; Susan C. Guba, Jingyi Liu, Bente Frimodt-Moller, and William J. John, Eli Lilly, Indianapolis, IN; Coleman K. Obasaju and Eduardo J. Pennella, Lilly USA, Indianapolis, IN; and Ramaswamy Govindan, Washington University School of Medicine, St. Louis, MO.
authors.forename: Jyoti D
authors.initials: JD
authors.lastname: Patel
authors.forename: Mark A
authors.initials: MA
authors.lastname: Socinski
authors.forename: Edward B
authors.initials: EB
authors.lastname: Garon
authors.forename: Craig H
authors.initials: CH
authors.lastname: Reynolds
authors.forename: David R
authors.initials: DR
authors.lastname: Spigel
authors.forename: Mark R
authors.initials: MR
authors.lastname: Olsen
authors.forename: Robert C
authors.initials: RC
authors.lastname: Hermann
authors.forename: Robert M
authors.initials: RM
authors.lastname: Jotte
authors.forename: Thaddeus
authors.initials: T
authors.lastname: Beck
authors.forename: Donald A
authors.initials: DA
authors.lastname: Richards
authors.forename: Susan C
authors.initials: SC
authors.lastname: Guba
authors.forename: Jingyi
authors.initials: J
authors.lastname: Liu
authors.forename: Bente
authors.initials: B
authors.lastname: Frimodt-Moller
authors.forename: William J
authors.initials: WJ
authors.lastname: John
authors.forename: Coleman K
authors.initials: CK
authors.lastname: Obasaju
authors.forename: Eduardo J
authors.initials: EJ
authors.lastname: Pennella
authors.forename: Philip
authors.initials: P
authors.lastname: Bonomi
authors.forename: Ramaswamy
authors.initials: R
authors.lastname: Govindan
mesh_terms: D000368:Aged; 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* / Q000401:mortality / Q000473:pathology; D004334:Drug Administration Schedule; D005260:Female; D005971:Glutamates / Q000008:administration & dosage; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage; D000068437:Pemetrexed; D016016:Proportional Hazards Models; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D005971:Glutamates; D000068437:Pemetrexed; D000068258:Bevacizumab; D006147:Guanine; D016190:Carboplatin; D017239:Paclitaxel