Lapatinib versus hormone therapy in patients with advanced renal cell carcinoma: a randomized phase III clinical trial.

2.50
Hdl Handle:
http://hdl.handle.net/10541/66158
Title:
Lapatinib versus hormone therapy in patients with advanced renal cell carcinoma: a randomized phase III clinical trial.
Authors:
Ravaud, Alain; Hawkins, Robert E; Gardner, Jason P; Von der Maase, Hans; Zantl, Niko; Harper, P; Rolland, Frédéric; Audhuy, Bruno; Machiels, Jean-Pascal; Pétavy, Frank; Gore, Martin; Schöffski, Patrick; El-Hariry, Iman
Abstract:
PURPOSE: 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. PATIENTS AND 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%). CONCLUSION: 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.
Affiliation:
Department of Medical Oncology, Hôpital Saint André, CHU Bordeaux, 1 rue Jean Burguet, 33075 Bordeaux cedex, France. alain.ravaud@chu-bordeaux.fr
Citation:
Lapatinib versus hormone therapy in patients with advanced renal cell carcinoma: a randomized phase III clinical trial. 2008, 26 (14):2285-91 J. Clin. Oncol.
Journal:
Journal of Clinical Oncology
Issue Date:
10-May-2008
URI:
http://hdl.handle.net/10541/66158
DOI:
10.1200/JCO.2007.14.5029
PubMed ID:
18467719
Type:
Article
Language:
en
ISSN:
1527-7755
Appears in Collections:
All Paterson Institute for Cancer Research; Medical Oncology

Full metadata record

DC FieldValue Language
dc.contributor.authorRavaud, Alain-
dc.contributor.authorHawkins, Robert E-
dc.contributor.authorGardner, Jason P-
dc.contributor.authorVon der Maase, Hans-
dc.contributor.authorZantl, Niko-
dc.contributor.authorHarper, P-
dc.contributor.authorRolland, Frédéric-
dc.contributor.authorAudhuy, Bruno-
dc.contributor.authorMachiels, Jean-Pascal-
dc.contributor.authorPétavy, Frank-
dc.contributor.authorGore, Martin-
dc.contributor.authorSchöffski, Patrick-
dc.contributor.authorEl-Hariry, Iman-
dc.date.accessioned2009-04-24T09:14:51Z-
dc.date.available2009-04-24T09:14:51Z-
dc.date.issued2008-05-10-
dc.identifier.citationLapatinib versus hormone therapy in patients with advanced renal cell carcinoma: a randomized phase III clinical trial. 2008, 26 (14):2285-91 J. Clin. Oncol.en
dc.identifier.issn1527-7755-
dc.identifier.pmid18467719-
dc.identifier.doi10.1200/JCO.2007.14.5029-
dc.identifier.urihttp://hdl.handle.net/10541/66158-
dc.description.abstractPURPOSE: 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. PATIENTS AND 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%). CONCLUSION: 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.en
dc.language.isoenen
dc.subjectKidney Canceren
dc.subjectRandomized Controlled Trialen
dc.subject.meshAdult-
dc.subject.meshAged-
dc.subject.meshAged, 80 and over-
dc.subject.meshAntineoplastic Agents, Hormonal-
dc.subject.meshCarcinoma, Renal Cell-
dc.subject.meshDisease-Free Survival-
dc.subject.meshFemale-
dc.subject.meshHumans-
dc.subject.meshImmunohistochemistry-
dc.subject.meshKidney Neoplasms-
dc.subject.meshMale-
dc.subject.meshMegestrol Acetate-
dc.subject.meshMiddle Aged-
dc.subject.meshProspective Studies-
dc.subject.meshProtein Kinase Inhibitors-
dc.subject.meshQuinazolines-
dc.subject.meshReceptor, Epidermal Growth Factor-
dc.subject.meshTamoxifen-
dc.titleLapatinib versus hormone therapy in patients with advanced renal cell carcinoma: a randomized phase III clinical trial.en
dc.typeArticleen
dc.contributor.departmentDepartment of Medical Oncology, Hôpital Saint André, CHU Bordeaux, 1 rue Jean Burguet, 33075 Bordeaux cedex, France. alain.ravaud@chu-bordeaux.fren
dc.identifier.journalJournal of Clinical Oncologyen

Related articles on PubMed

All Items in Christie are protected by copyright, with all rights reserved, unless otherwise indicated.