Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.


Combination therapy for advanced and metastatic kidney cancer

The treatment of metastatic kidney cancer is rapidly evolving with the shift from immune checkpoint inhibitor monotherapy to combination therapy. In 2018, the combination of nivolumab–ipilimumab received regulatory approval and multiple positive clinical trials were reported with combinations of PD-1 or PD-L1 inhibitors in conjunction with antiangiogenic drugs.

Key advances

  • The randomized phase III CheckMate 214 trial demonstrated that combination therapy with nivolumab–ipilimumab improved objective response rate (ORR) and overall survival (OS) compared with sunitinib3.

  • On the basis of CheckMate 214 (ref.3), the nivolumab–ipilimumab combination received regulatory approval for previously untreated patients with intermediate-risk or poor-risk advanced or metastatic clear cell renal cell carcinoma (ccRCC).

  • The randomized phase II IMmotion150 trial demonstrated promising progression-free survival (PFS) and ORR with the combination of atezolizumab and bevacizumab compared with sunitinib in programmed cell death 1 ligand 1 (PD-L1)+ patients4.

  • The single-arm phase Ib JAVELIN Renal 100 study demonstrated promising objective responses in previously untreated patients with ccRCC treated with avelumab plus axitinib6.

  • Pembrolizumab and axitinib demonstrated promising objective responses and PFS in a single-arm phase Ib trial in previously untreated patients with ccRCC8.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Get just this article for as long as you need it


Prices may be subject to local taxes which are calculated during checkout


  1. Choueiri, T. K. & Motzer, R. J. Systemic therapy for metastatic renal-cell carcinoma. N. Engl. J. Med. 376, 354–366 (2017).

    Article  CAS  Google Scholar 

  2. Carlo, M. I. et al. Checkpoint inhibitors and other novel immunotherapies for advanced renal cell carcinoma. Nat. Rev. Urol. 13, 420–431 (2016).

    Article  CAS  Google Scholar 

  3. Motzer, R. J. et al. Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma. N. Engl. J. Med. 378, 1277–1290 (2018).

    Article  CAS  Google Scholar 

  4. McDermott, D. F. 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. 24, 749–757 (2018).

    Article  CAS  Google Scholar 

  5. Motzer, R. J. et al. IMmotion151: a randomized phase III study of atezolizumab plus bevacizumab versus sunitinib in untreated metastatic renal cell carcinoma (mRCC) [abstract]. J. Clin. Oncol. 36 (Suppl. 6), 578 (2018).

    Article  Google Scholar 

  6. Choueiri, T. K. et al. Preliminary results for avelumab plus axitinib as first-line therapy in patients with advanced clear-cell renal-cell carcinoma (JAVELIN Renal 100): an open-label, dose-finding and dose-expansion, phase 1b trial. Lancet Oncol. 19, 451–460 (2018).

    Article  CAS  Google Scholar 

  7. Motzer, R. et al. JAVELIN renal 101: a randomized, phase III study of avelumab + axitinib versus sunitinib as first-line treatment of advanced renal cell carcinoma (aRCC) [abstract]. Ann. Oncol. 29 (Suppl. 8), LBA6_PR (2018).

    Google Scholar 

  8. Atkins, M. B. et al. Axitinib in combination with pembrolizumab in patients with advanced renal cell cancer: a non-randomised, open-label, dose-finding, and dose-expansion phase 1b trial. Lancet Oncol. 19, 405–415 (2018).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations


Corresponding author

Correspondence to Chung-Han Lee.

Ethics declarations

Competing interests

C.-H.L. has received consulting fees from Eisai and Exelixis, research money and/or grants from Bristol Myers Squibb, Calithera, Eisai, Exelixis and Pfizer. R.J.M. has received consulting fees from Pfizer, Genentech/Roche, Merck, Incyte, Eisai, Exelixis and Novartis, and research money and/or grants from Bristol Myers Squibb, Pfizer, Genentech/Roche and Eisai.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Lee, CH., Motzer, R.J. Combination therapy for advanced and metastatic kidney cancer. Nat Rev Urol 16, 77–78 (2019).

Download citation

  • Published:

  • Issue Date:

  • DOI:


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing