title: Quality-of-life and performance status results from the phase III RAINBOW study of ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated gastric or gastroesophageal junction adenocarcinoma.
abstract: BACKGROUND
  The phase III RAINBOW trial demonstrated that the addition of ramucirumab to paclitaxel improved overall survival, progression-free survival, and tumor response rate in fluoropyrimidine-platinum previously treated patients with advanced gastric/gastroesophageal junction (GEJ) adenocarcinoma. Here, we present results from quality-of-life (QoL) and performance status (PS) analyses.
  
  
  METHODS
  Patients with Eastern Cooperative Oncology Group PS of 0/1 were randomized to receive ramucirumab (8 mg/kg i.v.) or placebo on days 1 and 15 of a 4-week cycle, with both arms receiving paclitaxel (80 mg/m(2)) on days 1, 8, and 15. Patient-reported outcomes were assessed with the QoL/health status questionnaires EORTC QLQ-C30 and EQ-5D at baseline and 6-week intervals. PS was assessed at baseline and day 1 of every cycle. Time to deterioration (TtD) in each QLQ-C30 scale was defined as randomization to first worsening of ≥10 points (on 100-point scale) and TtD in PS was defined as first worsening to ≥2. Hazard ratios (HRs) for treatment effect were estimated using stratified Cox proportional hazards models.
  
  
  RESULTS
  Of the 665 patients randomized, 650 (98%) provided baseline QLQ-C30 and EQ-5D data, and 560 (84%) also provided data from ≥1 postbaseline time point. Baseline scores for both instruments were similar between arms. Of the 15 QLQ-C30 scales, 14 had HR < 1, indicating similar or longer TtD in QoL for ramucirumab + paclitaxel. Treatment with ramucirumab + paclitaxel was also associated with a delay in TtD in PS to ≥2 (HR = 0.798, P = 0.0941). Alternate definitions of PS deterioration yielded similar results: PS ≥ 3 (HR = 0.656, P = 0.0508), deterioration by ≥1 PS level (HR = 0.802, P = 0.0444), and deterioration by ≥2 PS levels (HR = 0.608, P = 0.0063). EQ-5D scores were comparable between treatment arms, stable during treatment, and worsened at discontinuation.
  
  
  CONCLUSIONS
  In patients with previously treated advanced gastric/GEJ adenocarcinoma, addition of ramucirumab to paclitaxel prolonged overall survival while maintaining patient QoL with delayed symptom worsening and functional status deterioration.
  
  
  BACKGROUND
  NCT01170663.
authors.affiliation: Institute of Clinical Cancer Research (IKF), UCT-University Cancer Center, Frankfurt, Germany albatran.salah@khnw.de.
authors.forename: S-E
authors.initials: SE
authors.lastname: Al-Batran
authors.affiliation: University Hospitals Gasthuisberg, Leuven, Belgium.
authors.forename: E
authors.initials: E
authors.lastname: Van Cutsem
authors.affiliation: Korea University Guro Hospital, Seoul, South Korea.
authors.forename: S C
authors.initials: SC
authors.lastname: Oh
authors.affiliation: Szent László Hospital, Budapest, Hungary.
authors.forename: G
authors.initials: G
authors.lastname: Bodoky
authors.affiliation: Division of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Shimada
authors.affiliation: Department of Clinical Trial Promotion, Chiba Cancer Center, Chiba, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Hironaka
authors.affiliation: Department of Clinical Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Sugimoto
authors.affiliation: Bashkortostan Clinical Oncology Center, Ufa, Russia.
authors.forename: O N
authors.initials: ON
authors.lastname: Lipatov
authors.affiliation: Department of Internal Medicine and Cancer Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: T-Y
authors.initials: TY
authors.lastname: Kim
authors.affiliation: Royal Marsden Hospital, Sutton, UK.
authors.forename: D
authors.initials: D
authors.lastname: Cunningham
authors.affiliation: Hôpital Européen Georges Pompidou, Université Paris V, Paris, France.
authors.forename: P
authors.initials: P
authors.lastname: Rougier
authors.affiliation: Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Muro
authors.affiliation: Eli Lilly and Company, Indianapolis, Indiana, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Liepa
authors.affiliation: Bayer HealthCare, Whippany, NJ, USA.
authors.forename: K
authors.initials: K
authors.lastname: Chandrawansa
authors.affiliation: Eli Lilly and Company, Bad Homburg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Emig
authors.affiliation: Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, Kashiwa, Chiba, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Ohtsu
authors.affiliation: Department of Oncology, Kliniken Essen Mitte Center of Pallative Care, Muenster University Clinic, Essen, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Wilke
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D018572:Disease-Free Survival; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004943:Esophagogastric Junction / Q000187:drug effects / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage*; D011788:Quality of Life; D016896:Treatment Outcome; D000096662:Ramucirumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D017239:Paclitaxel; D000096662:Ramucirumab
keywords: EORTC QLQ-C30; EQ-5D; GEJ cancer; gastric cancer; quality of life; ramucirumab