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Adjuvant Therapy for High Risk Localized Kidney Cancer: Emerging Evidence and Future Clinical Trials

2017; Lippincott Williams & Wilkins; Volume: 199; Issue: 1 Linguagem: Inglês

10.1016/j.juro.2017.04.092

1527-3792

Andrew T. Lenis, Nicholas M. Donin, David C. Johnson, Izak Faiena, Amirali Salmasi, Alexandra Drakaki, Arie S. Belldegrun, Allan J. Pantuck, Karim Chamie,

Bladder and Urothelial Cancer Treatments

No AccessJournal of UrologyReview Article1 Jan 2018Adjuvant Therapy for High Risk Localized Kidney Cancer: Emerging Evidence and Future Clinical Trials Andrew T. Lenis, Nicholas M. Donin, David C. Johnson, Izak Faiena, Amirali Salmasi, Alexandra Drakaki, Arie Belldegrun, Allan Pantuck, and Karim Chamie Andrew T. LenisAndrew T. Lenis Institute of Urologic Oncology, Department of Urology, University of California, Los Angeles, Los Angeles, California Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, California , Nicholas M. DoninNicholas M. Donin Institute of Urologic Oncology, Department of Urology, University of California, Los Angeles, Los Angeles, California Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, California , David C. JohnsonDavid C. Johnson Institute of Urologic Oncology, Department of Urology, University of California, Los Angeles, Los Angeles, California Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, California , Izak FaienaIzak Faiena Institute of Urologic Oncology, Department of Urology, University of California, Los Angeles, Los Angeles, California Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, California , Amirali SalmasiAmirali Salmasi Institute of Urologic Oncology, Department of Urology, University of California, Los Angeles, Los Angeles, California Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, California , Alexandra DrakakiAlexandra Drakaki Division of Hematology/Oncology, Department of Medicine, University of California, Los Angeles, Los Angeles, California , Arie BelldegrunArie Belldegrun Institute of Urologic Oncology, Department of Urology, University of California, Los Angeles, Los Angeles, California Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, California , Allan PantuckAllan Pantuck Institute of Urologic Oncology, Department of Urology, University of California, Los Angeles, Los Angeles, California Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, California , and Karim ChamieKarim Chamie Institute of Urologic Oncology, Department of Urology, University of California, Los Angeles, Los Angeles, California Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, California View All Author Informationhttps://doi.org/10.1016/j.juro.2017.04.092AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: We reviewed the literature on adjuvant therapies for patients with high risk localized kidney cancer following surgical resection. In this analysis we merge 2 recently published prospective trials with conflicting results within the context of their respective designs. In addition, we spotlight upcoming trials that use novel immunotherapy based checkpoint inhibitors and have the potential to establish a new standard of care. Materials and Methods: We searched PubMed® for English language articles published through January 2017 using the keywords "renal cell carcinoma," "kidney cancer," "immunotherapy," "targeted therapy" and "adjuvant therapy." ClinicalTrials.gov was queried for ongoing studies. Relevant data recently presented at major urology and medical oncology meetings are also included. Results: Adjuvant therapies for high risk localized kidney cancer can be grouped into the categories of 1) traditional immunotherapy, 2) inhibitors of the vascular endothelial growth factor and mTOR (mammalian target of rapamycin) pathways, 3) vaccines and antibody dependent cytotoxic agents, and 4) immune checkpoint inhibitors. Several trials of traditional immunotherapy, such as interferon-α and high dose interleukin-2, failed to demonstrate benefit as adjuvant treatment and were associated with significant adverse events. Vascular endothelial growth factor and mTOR inhibitors have less severe toxicity in metastatic disease and, therefore, are natural considerations for adjuvant trials. However, current data are conflicting. The ASSURE (Sunitinib Malate or Sorafenib Tosylate in Treating Patients with Kidney Cancer that was Removed by Surgery, NCT00326898) trial found no recurrence-free survival benefit of sorafenib or sunitinib over placebo, while S-TRAC (Clinical Trial Comparing Efficacy and Safety of Sunitinib versus Placebo for the Treatment of Patients at High Risk of Recurrent Renal Cell Cancer, NCT00375674) revealed that 1 year of sunitinib improved recurrence-free survival by 1.2 years. Vaccine based treatments and antibody dependent cytotoxic agents have had mixed results. New trials evaluating immune checkpoint inhibitors are planned, given the impressive efficacy and tolerability as second line agents in metastatic disease. Future adjuvant trials are likely to be guided by molecular signatures to treat patients most likely to benefit. Conclusions: Based on the available data, there appears to be no role for traditional immunotherapy as adjuvant treatment in patients with high risk localized kidney cancer following surgical resection. S-TRAC provides evidence that 1 year of adjuvant sunitinib in patients with higher risk locoregional disease increases the median time to recurrence. However, the data on overall survival are immature and adverse effects are common. Results from trials investigating immune checkpoint inhibitors are highly anticipated. References 1 : Five-year survival after surgical treatment for kidney cancer: a population-based competing risk analysis. Cancer2007; 109: 1763. Google Scholar 2 : Prognostic indicators for renal cell carcinoma: a multivariate analysis of 643 patients using the revised 1997 TNM staging criteria. J Urol2000; 163: 1090. Link, Google Scholar 3 : Outcomes and clinicopathologic variables associated with late recurrence after nephrectomy for localized renal cell carcinoma. 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Volume 199Issue 1January 2018Page: 43-52Supplementary Materials Advertisement Copyright & Permissions© 2018 by American Urological Association Education and Research, Inc.Keywordsrenal cellcarcinomaadjuvantskidney neoplasmsimmunologicMetricsAuthor Information Andrew T. Lenis Institute of Urologic Oncology, Department of Urology, University of California, Los Angeles, Los Angeles, California Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, California More articles by this author Nicholas M. Donin Institute of Urologic Oncology, Department of Urology, University of California, Los Angeles, Los Angeles, California Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, California More articles by this author David C. Johnson Institute of Urologic Oncology, Department of Urology, University of California, Los Angeles, Los Angeles, California Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, California More articles by this author Izak Faiena Institute of Urologic Oncology, Department of Urology, University of California, Los Angeles, Los Angeles, California Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, California More articles by this author Amirali Salmasi Institute of Urologic Oncology, Department of Urology, University of California, Los Angeles, Los Angeles, California Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, California More articles by this author Alexandra Drakaki Division of Hematology/Oncology, Department of Medicine, University of California, Los Angeles, Los Angeles, California More articles by this author Arie Belldegrun Institute of Urologic Oncology, Department of Urology, University of California, Los Angeles, Los Angeles, California Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, California More articles by this author Allan Pantuck Institute of Urologic Oncology, Department of Urology, University of California, Los Angeles, Los Angeles, California Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, California More articles by this author Karim Chamie Institute of Urologic Oncology, Department of Urology, University of California, Los Angeles, Los Angeles, California Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, California More articles by this author Expand All Advertisement PDF downloadLoading ...