memo - Magazine of European Medical Oncology

, Volume 12, Issue 4, pp 334–338 | Cite as

First-line treatment of metastatic renal cell carcinoma: current standard of care

  • Martin MarszalekEmail author
short review


The introduction of immune checkpoint inhibitors has further improved response and survival rates in patients with metastatic renal cell carcinoma. In this context, the most promising trial results in the past 12 months include KEYNOTE 426 and the 30-month update of CheckMate 214. Both trials, similar to IMmotion 151 and JAVELIN Renal 101, reported improved survival and response data. CheckMate 214 reported an overall survival benefit in intermediate and poor risk patients, however, such benefit was observed irrespective of conventional risk groups in KEYNOTE 426. These results prompted the European Association of Urology (EAU) to update their guidelines on the treatment of metastatic renal cell carcinoma and to recommend the combinations pembrolizumab/axitinib and nivolumab/ipilimumab as standard of care in previously untreated intermediate and poor risk patients and the combination pembrolizumab/axitinib as standard of care in previously untreated favorable risk patients. Inflammatory and angiogenic markers profiles may have the potential to become a tool aiding to better individualize treatment regimens in the future. Exploratory analyses of the IMmotion 151 trial present first results supporting such approach. Sarcomatoid variant histology remains an unfavorable prognostic parameter. Subgroup analyses of CheckMate 214 revealed exceptional response in patients with sarcomatoid histology. Whereas conventional therapy was inferior in such patients, more than 50% of patients responded to combined checkpoint inhibitor therapy. Increasing evidence points towards a crucial role of the gut microbiome in the response of patients to modern immune therapies. Any antibiotic treatment prior to the inition of immune checkpoint therapy can have detrimental impact on the intestinal microbiome, thereby dramatically reducing response rate to checkpoint inhibitors.


Combination Immune therapy Metastatic Keynote Checkmate 



Confidence interval


Combined positive score


Cytotoxic T lymphocyte associated protein 4


Hazard ratio


Metastatic renal cell carcinoma


Programmed cell death protein 1


Programmed cell death 1 ligand 1


Progression-free survival


Renal cell carcinoma


Tyrosine kinase inhibitor


Vascular endothelial growth factor


Conflict of interest

M. Marszalek serves as an advisor for Pfizer, Bristol Myer Squibb, Eusa Pharma, Eisai.


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Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Urology and AndrologySozialmedizinisches Zentrum Ost—DonauspitalViennaAustria

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