title: Lapatinib versus hormone therapy in patients with advanced renal cell carcinoma: a randomized phase III clinical trial.
abstract: OBJECTIVE
  Lapatinib is an orally reversible inhibitor of epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor 2 (HER-2) tyrosine kinases with demonstrated activity in patients with HER-2-positive breast cancer. In the current phase III open-label trial, lapatinib was compared with hormone therapy (HT) in patients with advanced renal cell carcinoma (RCC) that express EGFR and/or HER-2.
  
  
  METHODS
  Patients with advanced RCC who had experienced disease progression through first-line cytokine therapy--stratified by Karnofsky performance status and number of metastatic sites--were randomly assigned to lapatinib 1,250 mg daily or HT. The primary end point was time to progression (TTP); secondary end points included overall survival (OS), safety, and biomarker analyses.
  
  
  RESULTS
  Four hundred sixteen patients were enrolled onto the study. Median TTP was 15.3 weeks for lapatinib versus 15.4 weeks for HT (hazard ratio [HR] = 0.94; P = .60), and median OS was 46.9 weeks for lapatinib versus 43.1 weeks for HT (HR = 0.88; P = .29). In a biomarker analysis of patients with EGFR-overexpressed tumors (3+ by immunohistochemistry [IHC]; n = 241) median TTP was 15.1 weeks for lapatinib versus 10.9 weeks for HT (HR = 0.76; P = .06), and median OS was 46.0 weeks for lapatinib versus 37.9 weeks for HT (HR = 0.69; P = .02). These results were confirmed by Cox regression analysis. No unexpected toxicities were observed; the most commonly reported drug-related adverse events (all grades) for lapatinib were rash (44%) and diarrhea (40%).
  
  
  CONCLUSIONS
  Lapatinib was well tolerated with equivalent overall efficacy to HT in advanced RCC patients who had experienced disease progression while receiving cytokines, and the study supports that lapatinib prolonged OS relative to HT in patients with 3+ EGFR status determined by IHC.
authors.affiliation: Department of Medical Oncology, Hôpital Saint André, CHU Bordeaux, 1 rue Jean Burguet, 33075 Bordeaux cedex, France. alain.ravaud@chu-bordeaux.fr
authors.forename: Alain
authors.initials: A
authors.lastname: Ravaud
authors.forename: Robert
authors.initials: R
authors.lastname: Hawkins
authors.forename: Jason P
authors.initials: JP
authors.lastname: Gardner
authors.forename: Hans
authors.initials: H
authors.lastname: von der Maase
authors.forename: Niko
authors.initials: N
authors.lastname: Zantl
authors.forename: Peter
authors.initials: P
authors.lastname: Harper
authors.forename: Frédéric
authors.initials: F
authors.lastname: Rolland
authors.forename: Bruno
authors.initials: B
authors.lastname: Audhuy
authors.forename: Jean-Pascal
authors.initials: JP
authors.lastname: Machiels
authors.forename: Frank
authors.initials: F
authors.lastname: Pétavy
authors.forename: Martin
authors.initials: M
authors.lastname: Gore
authors.forename: Patrick
authors.initials: P
authors.lastname: Schöffski
authors.forename: Iman
authors.initials: I
authors.lastname: El-Hariry
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000201:enzymology; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D000077341:Lapatinib; D008297:Male; D019290:Megestrol Acetate / Q000627:therapeutic use; D008875:Middle Aged; D011446:Prospective Studies; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011799:Quinazolines / Q000627:therapeutic use*; D013629:Tamoxifen / Q000627:therapeutic use
chemical_list: D018931:Antineoplastic Agents, Hormonal; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D013629:Tamoxifen; D000077341:Lapatinib; D066246:ErbB Receptors; D019290:Megestrol Acetate