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Lapatinib Versus Hormone Therapy in Patients With Advanced Renal Cell Carcinoma: A Randomized Phase III Clinical Trial

Alain Ravaud, Robert Hawkins, Jason P. Gardner, Hans von der Maase, Niko Zantl, Peter Harper, Frédéric Rolland, Bruno Audhuy, Jean-Pascal Machiels, Frank Pétavy, Martin Gore, Patrick Schöffski, Iman El-Hariry

From the Department of Medical Oncology, Hôpital Saint André, Bordeaux; Department of Medical Oncology, Centre René Gauducheau, St Herblain; Department of Medical Oncology, Hôpital Pasteur, Colmar, France; Department of Medical Oncology, Christie Hospital, Manchester; GlaxoSmithKline, Greenford; Department of Medical Oncology, Guys and St Thomas's Hospitals; Department of Medical Oncology, Royal Marsden Hospital, London, United Kingdom; Department of Medical Oncology, Rigshospital, Copenhagen, Denmark; Department of Medical Oncology, Technische Universität München, München, Germany; Department of Medical Oncology, Université Catholique de Louvain, Brussels; and Department of Medical Oncology, Universitair Zeikenhuis Gasthuisberg, Leuven, Belgium

Corresponding author: Alain Ravaud, MD, PhD, Department of Medical Oncology, Hôpital Saint André, CHU Bordeaux, 1 rue Jean Burguet, 33075 Bordeaux cedex, France; e-mail: alain.ravaud{at}chu-bordeaux.fr

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.

Both A.R. and R.H. contributed equally to this work.

Presented at the 42nd Annual Meeting of the American Society of Clinical Oncology, June 2-6, 2006, Atlanta, GA.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.