Treatment Algorithm for Metastatic Renal Cell Carcinoma - Recommendations Based on Evidence and Clinical Practice

Bergmann, Lothar; Beck, J L; Bothe, Kathrin; Brinkmann, Olaf Anselm; Buse, Stephan; Goebell, Peter J.; Grünwald, Viktor; Holzapfel, Konstantin; Kübler, Hubert; Marschner, Norbert; Mickisch, G.; Schultze-Seemann, Wolfgang; Siebels, M.; Siemer, S.; Störkel, Stephan; Gschwend, Jürgen E.

doi:10.1159/000360179

Cited by 14 publications

(12 citation statements)

References 19 publications

(27 reference statements)

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“…Einigkeit besteht unter den Experten darüber, dass eine Therapie bei klinisch relevanter Progression indiziert ist. Es gibt jedoch keine eindeutig definierten Kriterien für das Ausmaß der Progression, die zum Therapiebeginn führen soll [25,26]. [28,29].…”

Section: Beginn Der Therapieunclassified

Interdisziplinäre Empfehlungen zur Behandlung des metastasierten Nierenzellkarzinoms

et al. 2017

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Thanks to the use of targeted therapies, the prognosis of patients with metastatic renal cell carcinoma (mRCC) has improved significantly. A median overall survival of more than 2 years is a realistic claim. These improvements are also reflected in recent discussions about 3 and more lines of therapy.Sunitinib, pazopanib, the combination of bevacizumab and interferon alpha, and temsirolimus are approved for first-line therapy of mRCC. Sunitinib and pazopanib are also approved for second-line therapy, which, for pazopanib, is confined to the use after cytokine failure. Everolimus (after tyrosine kinase inhibitor (TKI) treatment), sorafenib (after cytokines) and axitinib (after treatment with sunitinib or cytokines) are other compounds available for second-line therapy.3 new substances have recently been approved for second-line therapy: Nivolumab, cabozantinib, and lenvatinib combined with everolimus can be used after VEGF-targeted treatment has failed. It is for the first time that targeted immunotherapy and a combination of targeted substances are available for the treatment of mRCC.There is no new insight as to an optimal sequence therapy. Study results from a phase III trial suggest that the sequences sorafenib-sunitinib and sunitinib-sorafenib are equally effective.The purpose of an interdisciplinary expert meeting on RCC was to work out joint treatment recommendations based on current data and clinical experience and to integrate them into clinical routine practice. The results are presented in this publication.

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Section: Beginn Der Therapieunclassified

Interdisziplinäre Empfehlungen zur Behandlung des metastasierten Nierenzellkarzinoms

et al. 2017

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Section: Beginn Der Therapieunclassified

Interdisziplinäre Empfehlungen zur Behandlung des metastasierten Nierenzellkarzinoms

et al. 2017

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ZusammenfassungDie Prognose von Patienten mit einem metastasierten Nierenzellkarzinom (mRCC) hat sich dank zielgerichteter Substanzen deutlich verbessert. Überlebenszeiten von mehr als 2 Jahren sind realistisch. Die Fortschritte zeigen sich auch darin, dass zunehmend Therapieoptionen in Dritt- und weiteren Linien thematisiert werden.Sunitinib, Pazopanib, die Kombination Bevacizumab+Interferon-alpha sowie Temsirolimus sind für die Erstlinie beim mRCC zugelassen. Sunitinib und Pazopanib haben eine Zulassung auch für die Zweitlinientherapie – für Pazopanib ist diese auf den Einsatz nach Zytokinen beschränkt. Everolimus (nach Therapie mit einem Tyrosinkinase-Inhibitor; TKI), Axitinib (nach Sunitinib- oder Zytokintherapie) sowie Sorafenib (nach Zytokintherapie) sind weitere Wirkstoffe für die Zweitlinien-Therapie.In der Zweitlinientherapie gab es 3 Neuzulassungen: Nach Versagen einer gegen VEGF gerichteten Therapie können nun Nivolumab, Cabozantinib und Lenvatinib in Kombination mit Everolimus eingesetzt werden. Damit stehen zum ersten Mal eine zielgerichtete Immuntherapie und eine Kombination zielgerichteter Substanzen beim mRCC zur Verfügung.Zur Frage nach der optimalen Sequenztherapie gibt es keine neuen Erkenntnisse. Bisher liegen Ergebnisse einer Phase-III-Studie vor, in der die geprüften Sequenzen Sorafenib-Sunitinib und Sequenz Sunitinib-Sorafenib gleichwertig waren.Ziel eines interdisziplinären RCC-Expertengesprächs war es, gemeinsame Therapieempfehlungen auf Basis der aktuell publizierten Daten und der eigenen klinischen Erfahrung zu erarbeiten und für den Praxisalltag abzuleiten. Die Ergebnisse werden in dieser Publikation vorgestellt.

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“…Although sunitinib is used for many patients with metastatic clear cell RCC, clinical practice guidelines recommend temsirolimus for the treatment of the RCC patients of any histology (clear and non-clear) with poor prognostic factors. 45 Temsirolimus is also standard care of therapy for patients with RCC, which has progressed after VEGFR-TKI therapy. 46 Since no consensus has been reached as to which of the mTOR pathway-related molecules predicts responsiveness to mTOR inhibitors, 47 there is an increasing demand for predicting biomarkers to select patients that are likely to benefit from the treatment.…”

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confidence: 99%

“…mTOR inhibition plays an important role in the targeted treatment of various cancers including RCC, and temsirolimus and everolimus are approved as therapeutic options for the treatment of RCC. Although sunitinib is used for many patients with metastatic clear cell RCC, clinical practice guidelines recommend temsirolimus for the treatment of the RCC patients of any histology (clear and non‐clear) with poor prognostic factors . Temsirolimus is also standard care of therapy for patients with RCC, which has progressed after VEGFR‐TKI therapy .…”

Section: Introductionmentioning

confidence: 99%

Recent advances in renal cell carcinoma from a pathological point of view

Mikami

Oya

Mizuno

et al. 2016

Pathology International

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The purpose of this article is to review the recent advances in renal cell carcinoma (RCC) from a pathological point of view. Because the genetic features and morphological characteristics have become major criteria for the classification of RCC, special techniques, such as immunohistochemistry, are essential to the differential diagnosis of renal tumors. Metastasis is frequently observed among the RCC patients with curative nephrectomy, and extracellular matrix-degrading enzymes, such as matrix metalloproteinases (MMP) and heparanase, play a key role in invasion and metastasis of RCC. Snail and Slug, transcription factors of epithelial-mesenchymal transition (EMT), accelerate cancer cell invasion through downregulation of E-cadherin and up-regulation of MMP. Therapies targeted at the vascular endothelial growth factor pathway have become the standard treatment of metastatic RCC. Although they lead to tumor shrinkage mainly by inhibiting angiogenesis, they have typically been associated with drug resistance. The mechanism of the resistance remains largely unknown, but complex events including re-activation of angiogenesis, EMT and cancer stem cells, and immune escape are implicated in the refractory response to the therapy. Recent advances of the research on RCC have caused the changes of classification and therapy, and pathologists should take overall view of these as integrated pathology.

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Treatment Algorithm for Metastatic Renal Cell Carcinoma - Recommendations Based on Evidence and Clinical Practice

Cited by 14 publications

References 19 publications

Interdisziplinäre Empfehlungen zur Behandlung des metastasierten Nierenzellkarzinoms

Interdisziplinäre Empfehlungen zur Behandlung des metastasierten Nierenzellkarzinoms

Interdisziplinäre Empfehlungen zur Behandlung des metastasierten Nierenzellkarzinoms

Recent advances in renal cell carcinoma from a pathological point of view

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