title: Class III β-tubulin in advanced NSCLC of adenocarcinoma subtype predicts superior outcome in a randomized trial.
abstract: OBJECTIVE
  Platinum-based doublets are the cornerstone of treatment in advanced non-small-cell lung cancer (NSCLC) and often include vinorelbine or taxanes. A predictive biomarker is greatly needed to select chemotherapy-sensitive patients for these microtubule-interfering agents. Class III β-tubulin (TUBB3) has been shown of value in NSCLC, but evidence is not uniform. Accordingly, we explored the predictive role of TUBB3 in advanced NSCLC.
  
  
  METHODS
  Four hundred forty-three patients with advanced NSCLC were enrolled in a phase III trial and randomized to vinorelbine- or paclitaxel-containing chemotherapy. Immunohistochemical evaluation of TUBB3 status was mainly done on bioptic material and correlated to response rates, progression-free survival (PFS), overall survival (OS), quality of life (QOL), and toxicity.
  
  
  RESULTS
  Two hundred sixty-one (58.9%) patients had representative tissue samples for TUBB3 evaluation. Patients with TUBB3-negative adenocarcinomas had a significantly prolonged PFS and OS when compared with the opposite subgroup (7.87 vs. 6.83 months, P = 0.035 and 14.17 vs. 11.17 months, P = 0.018, respectively). Multivariate analyses revealed an HR of 1.55 (95% CI, 1.04-2.31, P = 0.032) for TUBB3-positive adenocarcinoma patients. TUBB3-negative adenocarcinoma patients showed a mean QOL decline of -18.25 points (95% CI, -4.28 to -32.22, P = 0.013) as compared with -3.86 (95% CI, -7.0 to 15.52, P = 0.5).
  
  
  CONCLUSIONS
  TUBB3 was of predictive value in adenocarcinoma patients in the largest, randomized advanced NSCLC population published to date. It may be clinically useful in conjunction with other biomarkers, but QOL information should be recorded during validation, as prophylactic intervention may be needed in specific subgroups at risk of toxicity.
authors.affiliation: Department of Oncology 5073, Finsen Centre, and Department of Pathology 5442, Diagnostic Center, National University Hospital, Copenhagen, Denmark. adamvilmar@hotmail.com
authors.forename: Adam Christian
authors.initials: AC
authors.lastname: Vilmar
authors.forename: Eric
authors.initials: E
authors.lastname: Santoni-Rugiu
authors.forename: Jens Benn
authors.initials: JB
authors.lastname: Sørensen
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000627:therapeutic use; D011379:Prognosis; D015996:Survival Rate; D016896:Treatment Outcome; D014404:Tubulin / Q000378:metabolism*; D014747:Vinblastine / Q000031:analogs & derivatives; D000077235:Vinorelbine
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C498585:TUBB3 protein, human; D014404:Tubulin; D014747:Vinblastine; D017239:Paclitaxel; D000077235:Vinorelbine