A Phase II,Single-arm Trial of Sunitinib and Erlotinib in Advanced Renal Cell Carcinoma |
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| Affiliation: | 1. Oregon Health and Science University Knight Cancer Institute, Portland, OR;2. Providence Cancer Institute, Portland, OR;3. University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA;4. Oregon Oncology Specialists, Salem, OR;1. Department of Urology and Pediatric Urology, University Hospital of Würzburg, Würzburg, Germany;2. Department of Urology, University Hospital of Tübingen, Germany;3. King Salman Hospital (MOH), Riyadh, Saudi-Arabia;1. Department of Surgical and Diagnostic Integrated Sciences (DISC), University of Genova, Genova, Italy;2. Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, Québec, Canada;3. Department of Urology, IRCCS Policlinico San Martino, Genova, Italy;4. Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany;5. Department of Maternal-Child and Urological Sciences, Sapienza Rome University, Policlinico Umberto I Hospital, Rome, Italy;6. Division of Experimental Oncology/Unit of Urology, URI, Urological Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy;7. Department of Urology, University Hospital Frankfurt, Frankfurt am Main, Germany;8. Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria;9. Departments of Urology, Weill Cornell Medical College, New York, NY;10. Department of Urology, University of Texas Southwestern, Dallas, TX;11. Department of Urology, Second Faculty of Medicine, Charles University, Prague, Czech Republic;12. Institute for Urology and Reproductive Health, I.M. Sechenov First Moscow State Medical University, Moscow, Russia;13. Division of Urology, Department of Special Surgery, Jordan University Hospital, The University of Jordan, Amman, Jordan;1. Latin American Cooperative Oncology Group – LACOG, Porto Alegre, RS, Brazil;2. Hospital Santa Lucia, Brasilia, DF, Brazil;3. Hospital Universitário de Brasília, Brasilia, DF, Brazil;4. Grupo SONHE, Campinas, SP, Brazil;5. Hospital Israelita Albert Einstein, São Paulo, SP, Brazil;6. Centro Paulista de Oncologia/Oncoclínicas, São Paulo, SP Brazil;7. Oncologia D''Or, Salvador, BA, Brazil;8. MD Anderson Cancer Center Madrid, Madrid, Spain;9. Oncology Unit, Macerata Hospital, Macerata, Italy;10. Pontifical Catholic University of Rio Grande do Sul, School of Medicine, Oncology Department, Porto Alegre, RS, Brazil;1. Department of Oncology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark;2. Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Copenhagen Denmark;3. International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC) University of Copenhagen, Copenhagen, Denmark;4. Department of Clinical Physiology, Nuclear Medicine and PET, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark;5. Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark;6. Centre of Physical Activity Research, Centre of Inflammation and Metabolism, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark;7. Statistics and Data analysis, Danish Cancer Society Research Center, Danish Cancer Society, Copenhagen, Denmark;1. Struttura Semplice Dipartimentale di Oncologia Medica per la Presa in Carico Globale del Paziente Oncologico "Don Tonino Bello," I.R.C.C.S. Istituto Tumori "Giovanni Paolo II," Bari, Italy;2. Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy;3. Oncology Unit, Macerata Hospital, Macerata, Italy;4. Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy;1. Department of Urology, Marien Hospital Herne, Ruhr-University Bochum, Herne, Germany;2. Center for Urological Rehabilitation, Kliniken Hartenstein, Bad Wildungen, Germany |
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| Abstract: | BackgroundOverexpression of the epidermal growth factor receptor (EGFR) and its ligands occur frequently in renal cell carcinoma (RCC). Combined vascular endothelial growth factor receptor (VEGF-R) and EGFR inhibition may overcome resistance to VEGF-R inhibitor monotherapy. We performed a dose-escalation phase II study of sunitinib plus erlotinib in advanced renal cell carcinoma.Patients and MethodsPatients with metastatic clear cell or papillary RCC were eligible. Prior therapy was allowed except sunitinib or erlotinib. Three dose levels of erlotinib (50, 100, 150 mg daily) were evaluated in combination with sunitinib 50 mg. Thirty-seven patients were treated at maximum tolerated dose to determine efficacy. The primary endpoint was 8-month progression-free survival (PFS) rate. The trial was powered to assess for a difference between a median PFS of less than 50% with a targeted 70% PFS for the combination.ResultsThe 8-month PFS rate was 40% (95% CI: 23-56). Median PFS was 5.8 months (95% CI: 4.1-9.7) and median overall survival (OS) was 26.3 months (95% CI: 16.1-34.0). The objective response rate was 22% and an additional 59% of patients had stable disease for at least 6 weeks. The most common adverse events for all grades were diarrhea, rash, fatigue, and dysgeusia. Dose reduction in 1 or both of the drugs was undertaken in 17 (46%) patients, while 5 (14%) discontinued study therapy due to toxicity.ConclusionWhile sunitinib and erlotinib are combinable,the 8-month PFS rate did not suggest efficacy improvement over sunitinib monotherapy (NCT00425386). |
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