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KIDNEY CANCER IN 2018

Combination therapy for advanced and metastatic kidney cancer

Nature Reviews Urology volume 16, pages 77–78 (2019)Cite this article

Subjects

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.

Systemic therapy for kidney cancer has developed rapidly since 2006 with the regulatory approval of 11 therapeutic agents, which can broadly be classified as vascular endothelial growth factor (VEGF) axis-targeted agents, mechanistic target of rapamycin (mTOR) pathway inhibitors or immune checkpoint inhibitors (ICIs)1,2. Most regimens have been used as monotherapy. In 2018, CheckMate 214 (ref.3) tested the combination of two ICIs and data from multiple early phase clinical trials evaluating novel combinations of ICIs in conjunction with VEGF-targeted therapy were published.

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References

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Authors and Affiliations

  1. Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Chung-Han Lee & Robert J. Motzer

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  1. Chung-Han Lee
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Correspondence to Chung-Han Lee.

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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.

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Lee, CH., Motzer, R.J. Combination therapy for advanced and metastatic kidney cancer. Nat Rev Urol 16, 77–78 (2019). https://doi.org/10.1038/s41585-018-0133-7

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