title: Bevacizumab for advanced cervical cancer: patient-reported outcomes of a randomised, phase 3 trial (NRG Oncology-Gynecologic Oncology Group protocol 240).
abstract: BACKGROUND
  GOG 240 was a practice-changing randomised phase 3 trial that concluded that chemotherapy plus bevacizumab for advanced cervical cancer significantly improves overall and progression-free survival, and the proportion of patients achieving an overall objective response, compared with chemotherapy alone. In this study, we aimed to analyse patient-reported outcomes in GOG 240.
  
  
  METHODS
  Eligible adult participants (aged ≥18 years) had primary stage IVB or recurrent or persistent carcinoma of the cervix with measurable disease and GOG performance status of 0-1. Participants were randomly assigned by web-based permuted block randomisation (block size 4) in a 1:1:1:1 ratio to the four treatment groups: cisplatin (50 mg/m(2) intravenously on day 1 or 2 of the treatment cycle) and paclitaxel (135 mg/m(2) intravenously over 24 h or 175 mg/m(2) intravenously over 3 h on day 1), with or without bevacizumab (15 mg/kg intravenously on day 1 or 2), or paclitaxel (175 mg/m(2) over 3 h on day 1) and topotecan (0·75 mg/m(2) for 30 min on days 1-3) with or without bevacizumab (15 mg/kg intravenously on day 1). Treatment assignment was concealed at randomisation (everyone was masked to treatment assignment, achieved by the use of a computer encrypted numbering system at the National Cancer Institute) and became open-label when each patient was registered to the trial. Treatment cycles were repeated every 21 days until disease progression or unacceptable toxicity, whichever occurred first. The coprimary endpoints of the trial were overall survival and safety; the primary quality-of-life endpoint was the score on the Functional Assessment of Cancer Therapy-Cervix Trial Outcome Index (FACT-Cx TOI). For our analysis of patient-reported outcomes, participants were assessed before treatment cycles 1, 2, and 5, and at 6 and 9 months after the start of cycle 1, with the FACT-Cx TOI, items from the FACT-GOG-Neurotoxicity subscale, and a worst pain item from the Brief Pain Inventory. All patients who completed baseline quality-of-life assessments and at least one further follow-up assessment were evaluable for quality-of-life outcomes. This study is registered with ClinicalTrials.gov, number NCT00803062.
  
  
  RESULTS
  Between April 6, 2009, and Jan 3, 2012, a total of 452 patients were enrolled in the trial, of whom 390 completed baseline quality-of-life assessment and at least one further assessment and were therefore evaluable for quality-of-life outcomes. In these patients, patient-reported outcome completion declined from 426 (94%) of 452 (at baseline) to 193 (63%) of 307 (9 months post-cycle 1), but completion rates did not differ significantly between treatment regimens (p=0·78). The baseline FACT-Cx TOI scores did not differ significantly between patients who received bevacizumab versus those who did not (p=0·27). Compared with patients who received chemotherapy alone, patients who received chemotherapy plus bevacizumab reported FACT-Cx TOI scores that were an average of 1·2 points lower (98·75% CI -4·1 to 1·7; p=0·30).
  
  
  CONCLUSIONS
  Improvements in overall survival and progression-free survival attributed to the incorporation of bevacizumab into the treatment of advanced cervical cancer were not accompanied by any significant deterioration in health-related quality of life. Patients responding to anti-angiogenesis therapy who maintain an acceptable quality of life could be suitable at progression for treatment with other novel therapies that might confer additional benefit.
  
  
  BACKGROUND
  National Institutes of Health.
authors: Division of Hematology and Oncology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA. Electronic address: rpenson@partners.org.
authors: Richard T
authors: RT
authors: Penson
authors: NRG Oncology/Gynecologic Oncology Group, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors: Helen Q
authors: HQ
authors: Huang
authors: University of California, Irvine Medical Center, Orange, CA, USA.
authors: Lari B
authors: LB
authors: Wenzel
authors: University of Arizona Cancer Center and Creighton University at St Joseph's Hospital and Medical Center, Phoenix, AZ, USA.
authors: Bradley J
authors: BJ
authors: Monk
authors: University of Iowa Hospitals, Iowa City, IA, USA.
authors: Sharon
authors: S
authors: Stockman
authors: Mayo Clinic, Rochester, MN, USA.
authors: Harry J
authors: HJ
authors: Long
authors: MD Anderson Cancer Center, Houston, TX, USA.
authors: Lois M
authors: LM
authors: Ramondetta
authors: Oklahoma University Health Science Center, Oklahoma City, OK, USA.
authors: Lisa M
authors: LM
authors: Landrum
authors: Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, Barcelona, Spain.
authors: Ana
authors: A
authors: Oaknin
authors: University of Cincinnati College of Medicine/Women's Cancer Center at Kettering, Kettering, OH, USA.
authors: Thomas J A
authors: TJ
authors: Reid
authors: Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors: Mario M
authors: MM
authors: Leitao
authors: Michiana Hematology Oncology PC-Mishawaka, Mishawaka, IN, USA.
authors: Michael
authors: M
authors: Method
authors: Indiana University School of Medicine, Indianapolis, IN, USA.
authors: Helen
authors: H
authors: Michael
authors: University of California, Irvine Medical Center, Orange, CA, USA.
authors: Krishnansu S
authors: KS
authors: Tewari
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D002277:Carcinoma / Q000098:blood supply* / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005060:Europe; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage; D016016:Proportional Hazards Models; D011788:Quality of Life; D012307:Risk Factors; D011795:Surveys and Questionnaires; D013997:Time Factors; D019772:Topotecan / Q000008:administration & dosage; D016896:Treatment Outcome; D014481:United States; D002583:Uterine Cervical Neoplasms / Q000098:blood supply* / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D019772:Topotecan; D017239:Paclitaxel; D002945:Cisplatin
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