title: Quality of life in patients with advanced non-small-cell lung cancer given maintenance treatment with pemetrexed versus placebo (H3E-MC-JMEN): results from a randomised, double-blind, phase 3 study.
abstract: BACKGROUND
  Pemetrexed maintenance therapy significantly improved overall survival and progression-free survival compared with placebo, and had a good safety profile in a phase 3 placebo-controlled study in patients with advanced non-small-cell lung cancer (NSCLC). Results for quality of life, symptom palliation, and tolerability are presented here.
  
  
  METHODS
  After four cycles of platinum-based induction therapy, 663 patients with stage IIIB or stage IV NSCLC and Eastern Cooperative Oncology Group performance status of 0 or 1 were randomly assigned (in a 2:1 ratio) from March 15, 2005, to July 20, 2007, using the Pocock and Simon minimisation method to receive pemetrexed (500 mg/m(2) every 21 days; n=441) or placebo (n=222) plus best supportive care until disease progression. The primary efficacy data have been reported previously. Patients completed the Lung Cancer Symptom Scale (LCSS) at baseline, after each cycle, and post-discontinuation. Worsening of symptoms was defined as an increase of 15 mm or more from baseline on a 100 mm scale for each LCSS item. The primary outcome for these quality-of-life analyses was time to worsening of symptoms, analysed for all randomised patients. This study is registered with ClinicalTrials.gov, number NCT00102804.
  
  
  RESULTS
  Baseline characteristics, including LCSS scores, were well balanced between groups. Baseline LCSS scores were low, indicating low symptom burden for patients without disease progression after completion of first-line treatment. Longer time to worsening was recorded for pain (hazard ratio [HR] 0·76, 95% CI 0·59-0·99; p=0·041) and haemoptysis (HR 0·58, 95% CI 0·34-0·97; p=0·038) with pemetrexed than with placebo; no other significant differences in analyses of time to worsening were noted. Additional longitudinal analyses showed a greater increase in loss of appetite in the pemetrexed group than in the placebo group (4·3 mm vs 0·2 mm; p=0·028). Rates of resource use were statistically higher for pemetrexed than for placebo: admissions to hospital for drug-related adverse events (19 [4%] vs none; p=0·001), transfusions (42 [10%] vs seven [3%]; p=0·003), and erythropoiesis-stimulating agents (26 [6%] vs four [2%]; p=0·017).
  
  
  CONCLUSIONS
  Quality of life during maintenance therapy with pemetrexed is similar to placebo, except for a small increase in loss of appetite, and significantly delayed worsening of pain and haemoptysis. In view of the improvements in overall and progression-free survival noted with pemetrexed maintenance therapy, such treatment is an option for patients with advanced non-squamous NSCLC who have not progressed after platinum-based induction therapy.
  
  
  BACKGROUND
  Eli Lilly.
authors.affiliation: Penn State Hershey Cancer Institute, Hershey, PA 17033, USA. cbelani@psu.edu
authors.forename: Chandra P
authors.initials: CP
authors.lastname: Belani
authors.forename: Thomas
authors.initials: T
authors.lastname: Brodowicz
authors.forename: Tudor E
authors.initials: TE
authors.lastname: Ciuleanu
authors.forename: Maciej
authors.initials: M
authors.lastname: Krzakowski
authors.forename: Sung Hyun
authors.initials: SH
authors.lastname: Yang
authors.forename: Fábio
authors.initials: F
authors.lastname: Franke
authors.forename: Branka
authors.initials: B
authors.lastname: Cucevic
authors.forename: Jayaprakash
authors.initials: J
authors.lastname: Madhavan
authors.forename: Armando
authors.initials: A
authors.lastname: Santoro
authors.forename: Rodryg
authors.initials: R
authors.lastname: Ramlau
authors.forename: Astra M
authors.initials: AM
authors.lastname: Liepa
authors.forename: Carla
authors.initials: C
authors.lastname: Visseren-Grul
authors.forename: Patrick
authors.initials: P
authors.lastname: Peterson
authors.forename: William J
authors.initials: WJ
authors.lastname: John
authors.forename: Christoph C
authors.initials: CC
authors.lastname: Zielinski
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001066:Appetite / Q000187:drug effects; D001208:Asia; D001938:Brazil; D002289:Carcinoma, Non-Small-Cell Lung / Q000150:complications / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000523:psychology; D018572:Disease-Free Survival; D004311:Double-Blind Method; D005060:Europe; D005260:Female; D005971:Glutamates / Q000009:adverse effects / Q000627:therapeutic use*; D006147:Guanine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006469:Hemoptysis / Q000209:etiology / Q000517:prevention & control; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000523:psychology; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000209:etiology / Q000517:prevention & control; D000068437:Pemetrexed; D016016:Proportional Hazards Models; D011788:Quality of Life; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States
chemical_list: D000964:Antimetabolites, Antineoplastic; D005971:Glutamates; D000068437:Pemetrexed; D006147:Guanine