title: Quality of life analyses from the randomized, open-label, phase III PointBreak study of pemetrexed-carboplatin-bevacizumab followed by maintenance pemetrexed-bevacizumab versus paclitaxel-carboplatin-bevacizumab followed by maintenance bevacizumab in patients with stage IIIB or IV nonsquamous non-small-cell lung cancer.
abstract: BACKGROUND
  Treatment impact on quality of life (QoL) informs treatment management decisions in advanced nonsquamous non-small-cell lung cancer (NS NSCLC). QoL outcomes from the phase III PointBreak trial are reported.
  
  
  METHODS
  Chemonaive patients (n = 939) with stage IIIB/IV nonsquamous non-small-cell lung cancer and Eastern Cooperative Oncology Group performance status 0 to 1 were randomized (1:1) to pemetrexed-carboplatin-bevacizumab (pemetrexed arm) or paclitaxel-carboplatin-bevacizumab (paclitaxel arm). Patients without progressive disease received maintenance pemetrexed-bevacizumab (pemetrexed arm) or bevacizumab (paclitaxel arm). QoL was assessed using Functional Assessment of Cancer Therapy (FACT)-General (FACT-G), FACT-Lung (FACT-L), and FACT/Gynecologic Oncology Group-Neurotoxicity (FACT-Ntx) instruments. Subscale scores, total scores, and trial outcome indices were analyzed using linear mixed-effects models. Post hoc analyses examined the association between baseline FACT scores and overall survival (OS).
  
  
  RESULTS
  Mean score differences in change from baseline significantly favored the pemetrexed arm for the neurotoxicity subscale score, FACT-Ntx total scores, and FACT-Ntx trial outcome index. They occurred at cycle 2 (p < 0.001) and persisted through induction cycles 2 to 4 and six maintenance cycles. Investigator-assessed, qualitative, drug-related differences in grade 2 (1.6% versus 10.6%) and grade 3 (0.0% versus 4.1%) sensory neuropathy and grade 3/4 fatigue (10.9% versus 5.0%, p = 0.0012) were observed between the pemetrexed and paclitaxel arms. Baseline FACT-G, FACT-L, and FACT-Ntx scores were significant prognostic factors for OS (p < 0.001).
  
  
  CONCLUSIONS
  Randomized patients reported similar changes in QoL, except for less change from baseline in neurotoxicity on the pemetrexed arm; investigators reported greater neurotoxicity on the paclitaxel arm and greater fatigue on the pemetrexed arm. Higher baseline FACT scores were favorable prognostic factors for OS.
authors.affiliation: *Sarah Cannon Research Institute/Tennessee Oncology, PLLC, Nashville, TN; †Feinberg School of Medicine, Northwestern University, Chicago, IL; ‡Ocala Oncology, Ocala, FL and US Oncology Research, Inc., Houston, TX; §David Geffen School of Medicine at UCLA/Translational Research in Oncology-US, Los Angeles, CA; ║Northwest Georgia Oncology Centers, Marietta, GA; ¶Washington University School of Medicine, St. Louis, MO; #Tulsa Cancer Institute, Tulsa, OK; **Eli Lilly and Company, Indianapolis, IN; ††University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA; and ‡‡Rush University Medical Center, Chicago, IL.
authors.forename: David R
authors.initials: DR
authors.lastname: Spigel
authors.forename: Jyoti D
authors.initials: JD
authors.lastname: Patel
authors.forename: Craig H
authors.initials: CH
authors.lastname: Reynolds
authors.forename: Edward B
authors.initials: EB
authors.lastname: Garon
authors.forename: Robert C
authors.initials: RC
authors.lastname: Hermann
authors.forename: Ramaswamy
authors.initials: R
authors.lastname: Govindan
authors.forename: Mark R
authors.initials: MR
authors.lastname: Olsen
authors.forename: Katherine B
authors.initials: KB
authors.lastname: Winfree
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
authors.forename: Jingyi
authors.initials: J
authors.lastname: Liu
authors.forename: Susan C
authors.initials: SC
authors.lastname: Guba
authors.forename: Mark A
authors.initials: MA
authors.lastname: Socinski
authors.forename: Philip
authors.initials: P
authors.lastname: Bonomi
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; 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; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage; D000068437:Pemetrexed; D011788:Quality of Life; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D005971:Glutamates; D000068437:Pemetrexed; D000068258:Bevacizumab; D006147:Guanine; D016190:Carboplatin; D017239:Paclitaxel