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.
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.
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Choueiri, T. K. & Motzer, R. J. Systemic therapy for metastatic renal-cell carcinoma. N. Engl. J. Med. 376, 354–366 (2017).
Carlo, M. I. et al. Checkpoint inhibitors and other novel immunotherapies for advanced renal cell carcinoma. Nat. Rev. Urol. 13, 420–431 (2016).
Motzer, R. J. et al. Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma. N. Engl. J. Med. 378, 1277–1290 (2018).
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).
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).
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).
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).
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).
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