Interdisciplinary recommendations for the treatment of metastatic renal cell carcinoma.

[Interdisciplinary recommendations for the treatment of metastatic renal cell carcinoma]. Aktuelle Urol. 2019 Sep 04;: Authors: Miller K, Bergmann L, Doehn C, Gschwend JE, Kuczyk MA Abstract Due to novel therapies, the prognosis of patients with metastatic renal cell carcinoma has improved significantly. A median overall survival of more than two years is a realistic goal. Immunotherapies with checkpoint inhibitors are new first-line and second-line options. Sunitinib, Pazopanib, Tivozanib and the combination of Bevacizumab + interferon alpha are approved for first-line therapy, regardless of the progression risk score. The use of both the combination Nivolumab + Ipilimumab and Cabozantinib is limited to intermediate and high-risk patients. In this subgroup, the immunotherapy combination was more effective in terms of overall survival compared with Sunitinib. Temsirolimus is only approved for high-risk patients. Sunitinib and Pazopanib can also be used as second-line options, with the use of Pazopanib being limited to the event of cytokine failure. Nivolumab and Cabozantinib demonstrated superior overall survival compared to Everolimus. Furthermore, the combination of Lenvatinib + Everolimus and Axitinib are approved treatment options in second-line and further settings. Everolimus monotherapy has been replaced by the new options. The question regarding the optimal sequence of treatments is still unanswered. An interdisciplinary expert meetin...
Source: Aktuelle Urologie - Category: Urology & Nephrology Authors: Tags: Aktuelle Urol Source Type: research

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This report outlines a translational PK-pharmacodynamic (PD) methodology used to derive a baseline composite cytokine signature correlated with nivolumab clearance using data from three clinical trials in which nivolumab or everolimus was administered.MethodsPeripheral serum cytokine (PD) and nivolumab clearance (PK) data from patients with RCC were analyzed using a PK-PD machine-learning model. Nivolumab studies CheckMate 009 (NCT01358721) and CheckMate 025 (NCT01668784) (n = 480) were used for PK-PD analysis model development and cytokine feature selection (training dataset). Validation of the model and asses...
Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
In the last decades, the prognosis of metastatic renal cell carcinoma (mRCC) has remarkably improved following the advent of the “targeted therapy” era. The expanding knowledge on the prominent role played by angiogenesis in RCC pathogenesis has led to approval of multiple anti-angiogenic agents such as sunitinib, pazopanib, axitinib, cabozantinib, sorafenib, and bevacizumab. These agents can induce radiological responses and delay cancer progression for months or years before onset of resistance, with a clinically meaningful activity. The need for markers of prognosis and efficacy of anti-angiogenic agents has...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Treatment with chimeric antigen receptor-modified T cell (CAR-T) has demonstrated promising therapeutic efficacy in hematologic malignancies. However, the therapeutic efficacy is still very limited for solid tumors. An immunosuppressive microenvironment is one of the main reasons for the limited efficacy. Some chemotherapeutic agents exhibit immune microenvironment modulation. Therefore, combination with chemotherapeutic agents may be one of the promising strategies to enhance the therapeutic efficacy of CAR-T against solid tumors. Sunitinib modulates the antitumor immune response by improving T-cell infiltration and funct...
Source: Journal of Immunotherapy - Category: Allergy & Immunology Tags: Basic Study Source Type: research
In conclusion, we described, for the first time, a case series of nivolumab-induced adrenal insufficiency in patients with mRCC. Our findings may be useful for the accurate diagnosis and the prompt treatment of this condition. In addition, there is a possibility that adrenal insufficiency may be associated with a favorable response to nivolumab in patients with mRCC.
Source: Journal of Immunotherapy - Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
CONCLUSION: The efficacy and tolerability of medical treatments for metastatic renal cancer have not been reported as different depending on age. No dosage adjustment is recommended in principle. However, prevention and early treatment of side effects of treatment should be strengthened in elderly patients. PMID: 31771770 [PubMed - in process]
Source: Progres en Urologie - Category: Urology & Nephrology Tags: Prog Urol Source Type: research
AbstractBackgroundImmune checkpoint inhibitors have achieved unprecedented success in cancer immunotherapy. With the exception of a few candidate biomarkers, the prognostic role of soluble immune checkpoint-related proteins in clear cell renal cell cancer (ccRCC) patients is largely uninvestigated.MethodsWe profiled the circulating levels of 14 immune checkpoint-related proteins panel (BTLA, GITR, HVEM, IDO, LAG-3, PD-1, PD-L1, PD-L2, Tim-3, CD28, CD80, CD137, CD27 and CTLA-4) and their associations with the risk of recurrence and death in 182 ccRCC patients using a multiplex Luminex assay. Gene expression in tumors from a...
Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
Publication date: Available online 25 November 2019Source: Urology Case ReportsAuthor(s): Kevin Zarrabi, Selma Masic, Christopher Schaefer, Michael J. Bartel, Alexander Kutikov, Matthew ZibelmanAbstractStauffer’s syndrome is a paraneoplastic phenomenon associated with renal cell carcinoma (RCC) characterized by cholestatic hepatitis. We explore the effects of perioperative immunotherapy in a case of Stauffer’s syndrome. A 70-year-old female with a locally advanced clear cell RCC (ccRCC) developed severe hyperbilirubinemia. The patient’s cholestasis progressed despite initial systemic immunotherapy, but im...
Source: Urology Case Reports - Category: Urology & Nephrology Source Type: research
Authors: Muto A, Gridelli C Abstract Introduction: Metastatic renal cell carcinoma (mRCC) in recent years has been one of the diseases in the oncology that has experienced the greatest development of targeted therapies.Area covered: On one hand, more and more refined acquisitions of molecular biology are allowing a better sub-classification of this tumor, identifying new and peculiar biological profiles of patients with metastatic renal cancer that will soon be destined for increasingly tailored treatments. On the other hand, immunotherapy has, in a short time, redesigned the perimeter of our knowledge, entering cl...
Source: Expert Opinion on Emerging Drugs - Category: Drugs & Pharmacology Tags: Expert Opin Emerg Drugs Source Type: research
We present in this case report, the abscopal effect observed in a 30-year-old Japanese woman with metastatic renal cell carcinoma after the treatment with high-dose-rate interstitial brachytherapy combined with nivolumab. This is the first published report demonstrating an abscopal effect following brachytherapy for human malignancy. Our case indicates that immuno-oncology effects are not limited to external beam irradiation regimens as they can also be attained by brachytherapy. PMID: 31749855 [PubMed]
Source: Journal of Contemporary Brachytherapy - Category: Cancer & Oncology Tags: J Contemp Brachytherapy Source Type: research
ConclusionsMultiple cytokines found in an immune-reactive TME may induce PD-L1 expression on tumor and/or immune cells through distinct signaling mechanisms. Factors driving constitutive PD-L1 expression were not identified in this study. Understanding complex mechanisms underlying PD-L1 display in the TME may allow treatment approaches mitigating expression of this immunosuppressive ligand, to enhance the impact of PD-1 blockade.
Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
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