Skip to main content
main-content

Tipp

Weitere Artikel dieser Ausgabe durch Wischen aufrufen

Erschienen in: memo - Magazine of European Medical Oncology 4/2019

21.11.2019 | short review

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

verfasst von: MD Assoc. Prof. Martin Marszalek

Erschienen in: memo - Magazine of European Medical Oncology | Ausgabe 4/2019

Einloggen, um Zugang zu erhalten
share
TEILEN

Summary

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.
Literatur
1.
Zurück zum Zitat Ljungberg B, Albiges L, Abu-Ghanem Y, et al. European Association of Urology guidelines on renal cell carcinoma: the 2019 update. Eur Urol. 2019;75:799–810. CrossRef Ljungberg B, Albiges L, Abu-Ghanem Y, et al. European Association of Urology guidelines on renal cell carcinoma: the 2019 update. Eur Urol. 2019;75:799–810. CrossRef
2.
Zurück zum Zitat Rini BI, Plimack ER, Stus V, et al. Pembrolizumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med. 2019;380:1116–27. CrossRef Rini BI, Plimack ER, Stus V, et al. Pembrolizumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med. 2019;380:1116–27. CrossRef
3.
Zurück zum Zitat Motzer RJ, Penkov K, Haanen J, et al. Avelumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med. 2019;380:1103–15. CrossRef Motzer RJ, Penkov K, Haanen J, et al. Avelumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med. 2019;380:1103–15. CrossRef
4.
Zurück zum Zitat Rini BI, Powles T, Atkins MB, et al. Atezolizumab plus bevacizumab versus sunitinib in patients with previously untreated metastatic renal cell carcinoma (IMmotion151): a multicentre, open-label, phase 3, randomised controlled trial. Lancet. 2019;393:2404–15. CrossRef Rini BI, Powles T, Atkins MB, et al. Atezolizumab plus bevacizumab versus sunitinib in patients with previously untreated metastatic renal cell carcinoma (IMmotion151): a multicentre, open-label, phase 3, randomised controlled trial. Lancet. 2019;393:2404–15. CrossRef
5.
Zurück zum Zitat Motzer RJ, Tannir NM, McDermott DF, et al. Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma. N Engl J Med. 2018;378:1277–90. CrossRef Motzer RJ, Tannir NM, McDermott DF, et al. Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma. N Engl J Med. 2018;378:1277–90. CrossRef
6.
Zurück zum Zitat Tannir N, Frontera O, Hammers H, et al. Thirty-month follow-up of the phase III CheckMate 214 trial of first-line nivolumab + ipilimumab (N+I) or sunitinib (S) in patients (pts) with advanced renal cell carcinoma (aRCC). J Clin Oncol. 2019;37:547. CrossRef Tannir N, Frontera O, Hammers H, et al. Thirty-month follow-up of the phase III CheckMate 214 trial of first-line nivolumab + ipilimumab (N+I) or sunitinib (S) in patients (pts) with advanced renal cell carcinoma (aRCC). J Clin Oncol. 2019;37:547. CrossRef
7.
Zurück zum Zitat McDermott DF, Huseni MA, Atkins MB, et al. Clinical activity and molecular correlates of response to atezolizumab alone or in combination with bevacizumab versus sunitinib in renal cell carcinoma. Nat Med. 2018;24:749–57. CrossRef McDermott DF, Huseni MA, Atkins MB, et al. Clinical activity and molecular correlates of response to atezolizumab alone or in combination with bevacizumab versus sunitinib in renal cell carcinoma. Nat Med. 2018;24:749–57. CrossRef
8.
Zurück zum Zitat Shuch B, Bratslavsky G, Linehan WM, Srinivasan R. Sarcomatoid renal cell carcinoma: a comprehensive review of the biology and current treatment strategies. Oncologist. 2012;17:46–54. CrossRef Shuch B, Bratslavsky G, Linehan WM, Srinivasan R. Sarcomatoid renal cell carcinoma: a comprehensive review of the biology and current treatment strategies. Oncologist. 2012;17:46–54. CrossRef
9.
Zurück zum Zitat Alevizakos M, Gaitanidis A, Nasioudis D, Msaouel P, Appleman LJ. Sarcomatoid renal cell carcinoma: population-based study of 879 patients. Clin Genitourin Cancer. 2019;17:e447–e53. CrossRef Alevizakos M, Gaitanidis A, Nasioudis D, Msaouel P, Appleman LJ. Sarcomatoid renal cell carcinoma: population-based study of 879 patients. Clin Genitourin Cancer. 2019;17:e447–e53. CrossRef
10.
Zurück zum Zitat Korenbaum C, Pierard L, Thiery A, et al. Treatments, outcomes, and validity of prognostic scores in patients with sarcomatoid renal cell carcinoma: a 20-year single-institution experience. Clin Genitourin Cancer. 2018;16:e577–e86. CrossRef Korenbaum C, Pierard L, Thiery A, et al. Treatments, outcomes, and validity of prognostic scores in patients with sarcomatoid renal cell carcinoma: a 20-year single-institution experience. Clin Genitourin Cancer. 2018;16:e577–e86. CrossRef
11.
Zurück zum Zitat McDermott D, Choueiri T, Motzer R, et al. CheckMate 214 post-hoc analyses of nivolumab plus ipilimumab or sunitinib in IMDC intermediate/poor-risk patients with previously untreated advanced renal cell carcinoma with sarcomatoid features. J Clin Oncol. 2019;37:4513. CrossRef McDermott D, Choueiri T, Motzer R, et al. CheckMate 214 post-hoc analyses of nivolumab plus ipilimumab or sunitinib in IMDC intermediate/poor-risk patients with previously untreated advanced renal cell carcinoma with sarcomatoid features. J Clin Oncol. 2019;37:4513. CrossRef
12.
Zurück zum Zitat Routy B, Le Chatelier E, Derosa L, et al. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science. 2018;359:91–7. CrossRef Routy B, Le Chatelier E, Derosa L, et al. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science. 2018;359:91–7. CrossRef
13.
Zurück zum Zitat Sivan A, Corrales L, Hubert N, et al. Commensal bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Science. 2015;350:1084–9. CrossRef Sivan A, Corrales L, Hubert N, et al. Commensal bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Science. 2015;350:1084–9. CrossRef
14.
Zurück zum Zitat Derosa L, Hellmann MD, Spaziano M, et al. Negative association of antibiotics on clinical activity of immune checkpoint inhibitors in patients with advanced renal cell and non-small-cell lung cancer. Ann Oncol. 2018;29:1437–44. CrossRef Derosa L, Hellmann MD, Spaziano M, et al. Negative association of antibiotics on clinical activity of immune checkpoint inhibitors in patients with advanced renal cell and non-small-cell lung cancer. Ann Oncol. 2018;29:1437–44. CrossRef
15.
Zurück zum Zitat Alexander JL, Wilson ID, Teare J, Marchesi JR, Nicholson JK, Kinross JM. Gut microbiota modulation of chemotherapy efficacy and toxicity. Nat Rev Gastroenterol Hepatol. 2017;14:356–65. CrossRef Alexander JL, Wilson ID, Teare J, Marchesi JR, Nicholson JK, Kinross JM. Gut microbiota modulation of chemotherapy efficacy and toxicity. Nat Rev Gastroenterol Hepatol. 2017;14:356–65. CrossRef
Metadaten
Titel
First-line treatment of metastatic renal cell carcinoma: current standard of care
verfasst von
MD Assoc. Prof. Martin Marszalek
Publikationsdatum
21.11.2019
Verlag
Springer Vienna
Erschienen in
memo - Magazine of European Medical Oncology / Ausgabe 4/2019
Print ISSN: 1865-5041
Elektronische ISSN: 1865-5076
DOI
https://doi.org/10.1007/s12254-019-00550-7

Weitere Artikel der Ausgabe 4/2019

memo - Magazine of European Medical Oncology 4/2019 Zur Ausgabe