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KIDNEY CANCER IN 2019

Evolution in upfront treatment strategies for metastatic RCC

Nature Reviews Urology volume 17, pages 73–74 (2020)Cite this article

Subjects

The treatment paradigm for treatment-naive metastatic clear cell renal cell carcinoma continued to evolve in 2019 as three phase III randomized controlled trials were reported comparing sunitinib with combination immune checkpoint inhibitors and VEGF-targeted therapy. Pembrolizumab plus axitinib and avelumab plus axitinib became new treatment options for untreated patients, irrespective of risk group or PD-L1 expression.

Key points

  • The KEYNOTE-426 trial2 demonstrated that combination therapy with pembrolizumab plus axitinib improved overall survival (OS), progression-free survival (PFS) and objective response rate (ORR) compared with sunitinib.

  • The JAVELIN Renal 101 trial3 demonstrated that the combination of avelumab plus axitinib improved PFS and ORR compared with sunitinib, but OS was not superior.

  • The IMmotion-151 trial4 demonstrated that atezolizumab plus bevacizumab improved investigator-assessed PFS but not blinded, centrally assessed PFS in PD-L1 positive patients, and OS was not improved compared with sunitinib.

  • The FDA and the EMA approved pembrolizumab plus axitinib and avelumab plus axitinib for treatment-naive metastatic clear cell renal cell carcinoma6,7,8,9.

  • Nivolumab as monotherapy has limited efficacy on untreated brain metastases5.

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Fig. 1: Evolution of first-line treatment strategies for metastatic and advanced clear cell renal cell carcinoma.

References

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  6. U.S. Food & Drug Administration. FDA approves pembrolizumab plus axitinib for advanced renal cell carcinoma. FDA https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-pembrolizumab-plus-axitinib-advanced-renal-cell-carcinoma (2019).

  7. U.S. Food & Drug Administration. FDA approves avelumab plus axitinib for renal cell carcinoma. FDA https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-avelumab-plus-axitinib-renal-cell-carcinoma (2019).

  8. European Medicine Agency. Summary of opinion (post authorisation): Keytruda, pembrolizumab. EMA https://www.ema.europa.eu/en/documents/smop/chmp-post-authorisation-summary-positive-opinion-keytruda-ii-69_en.pdf (2019).

  9. European Medicine Agency. Summary of opinion (post authorisation): Bavencio, avelumab. EMA https://www.ema.europa.eu/en/documents/smop/chmp-post-authorisation-summary-positive-opinion-bavencio-ii-09_en.pdf (2019).

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Authors and Affiliations

  1. University of Ottawa, Department of Medicine, Division of Medical Oncology, Ottawa, ON, Canada

    Dominick Bossé & Michael Ong

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  1. Dominick Bossé
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  2. Michael Ong
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Correspondence to Dominick Bossé.

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Competing interests

D.B. declares a consulting or advisory role with Bristol-Myers Squibb, Pfizer and AbbVie, and received honoraria from AstraZeneca, Ipsen, Amgen, AbbVie and Janssen. M.O. declares a consulting or advisory role and honoraria from Bristol-Myers Squibb, Merck, AstraZeneca, EMD-Serono, Sanofi, Jannsen, Astellas, Bayer, Abbvie and Pfizer, and has received research funding from AstraZeneca.

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Bossé, D., Ong, M. Evolution in upfront treatment strategies for metastatic RCC. Nat Rev Urol 17, 73–74 (2020). https://doi.org/10.1038/s41585-019-0271-6

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