Advertisement

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
  • 13 Downloads

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.

Keywords

Combination Immune therapy Metastatic Keynote Checkmate 

Abbreviations

CI

Confidence interval

CPS

Combined positive score

CTLA‑4

Cytotoxic T lymphocyte associated protein 4

HR

Hazard ratio

mRCC

Metastatic renal cell carcinoma

PD1

Programmed cell death protein 1

PDL1

Programmed cell death 1 ligand 1

PFS

Progression-free survival

RCC

Renal cell carcinoma

TKI

Tyrosine kinase inhibitor

VEGF

Vascular endothelial growth factor

Notes

Conflict of interest

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

References

  1. 1.
    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.CrossRefGoogle Scholar
  2. 2.
    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.CrossRefGoogle Scholar
  3. 3.
    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.CrossRefGoogle Scholar
  4. 4.
    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.CrossRefGoogle Scholar
  5. 5.
    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.CrossRefGoogle Scholar
  6. 6.
    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.CrossRefGoogle Scholar
  7. 7.
    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.CrossRefGoogle Scholar
  8. 8.
    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.CrossRefGoogle Scholar
  9. 9.
    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.CrossRefGoogle Scholar
  10. 10.
    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.CrossRefGoogle Scholar
  11. 11.
    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.CrossRefGoogle Scholar
  12. 12.
    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.CrossRefGoogle Scholar
  13. 13.
    Sivan A, Corrales L, Hubert N, et al. Commensal bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Science. 2015;350:1084–9.CrossRefGoogle Scholar
  14. 14.
    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.CrossRefGoogle Scholar
  15. 15.
    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.CrossRefGoogle Scholar

Copyright information

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

Authors and Affiliations

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

Personalised recommendations