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Review
. 2022 Jun;24(6):695-702.
doi: 10.1007/s11912-022-01196-1. Epub 2022 Mar 5.

Approaches to First-Line Therapy for Metastatic Clear Cell Renal Cell Carcinoma

Yu-Wei Chen  1   2 , Brian I Rini  3   4
Affiliations
Review

Approaches to First-Line Therapy for Metastatic Clear Cell Renal Cell Carcinoma

Yu-Wei Chen et al. Curr Oncol Rep. 2022 Jun.

Abstract

Purpose of review: Four immuno-oncology (IO)-based combinations have demonstrated overall survival benefit as frontline treatment of metastatic clear cell renal cell carcinoma (mccRCC). Choosing among the available combinations depends on treating physician's interpretation of existing data without level I evidence to inform choice of therapy. Landmark trials of mccRCC are reviewed and perspective on treatment options is provided.

Recent findings: The four IO-based combinations reviewed are ipilimumab/nivolumab (IO/IO), pembrolizumab/axitinib (IO/TKI), nivolumab/cabozantinib (IO/TKI), and pembrolizumab/lenvatinib (IO/TKI). The ipilimumab/nivolumab combination is notable for durable efficacy after extended 4-year follow-up. IO/TKI combinations have clinical efficacy across all IMDC risk groups with higher response rates and longer progression-free survival (PFS) but also had higher ≥ grade 3 adverse events rate. Patient tumor burden, performance status, and IMDC risk group are factors in choosing an IO-based treatment. IO/IO and IO/TKI combinations for mccRCC have distinct efficacy and toxicity profiles. Future studies are needed to identify biomarkers to optimize patient outcomes.

Keywords: First-line; Frontline; IO/IO; IO/TKI; Immune checkpoint inhibitor; Immuno-oncology; Immunotherapy; Kidney cancer; Renal cell carcinoma.

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Conflict of interest statement

Declarations

Conflict of interest Yu-Wei Chen declares that he has no conflict of interest. Brian I. Rini has received research funding (paid to his institution) from Pfizer, Hoffman-LaRoche, Incyte Corporation, AstraZeneca, TARIS Biomedical, Seattle Genetics, Arrowhead Pharmaceuticals, Immunomedics, Bristol-Myers Squibb, Mirati Therapeutics, Merck, Surface Oncology, Dragonfly Therapeutics, Aravive, and Exelixis; has received compensation for service as a consultant from Bristol-Myers Squibb, Pfizer, Genentech/Roche, Aveo Oncology, Synthorx, Compugen, Merck, Corvus Pharmaceuticals, Surface Oncology, 3D Medicines, Aravive, Alkermes, Arrowhead Pharmaceuticals, GlaxoSmithKline, Shionogi, Eisai, and NiKang Therapeutics; and owns stock in PTC Therapeutics.

References

    1. Motzer RJ, et al. Nivolumab versus everolimus in advanced renal-cell carcinoma. N Engl J Med. 2015;373(19):1803–13. - PMC - PubMed

    1. Motzer RJ, et al. Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma. N Engl J Med. 2018;378(14):1277–1290.

      CheckMate 214 demonstrated overall survival benefit of ipilimumab/nivolumab over sunitinib in advanced RCC.

    1. Rini BI, et al. Pembrolizumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med. 2019;380(12):1116–1127.

      Keynote 426 demonstrated overall survival benefit of pembrolizumab/axitinib over sunitinib in advanced RCC.

    1. Choueiri TK, et al. Nivolumab plus cabozantinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med. 2021;384(9):829–841.

      CheckMate 9ER demonstrated overall survival benefit of nivolumab/cabozantinib over sunitinib in advanced RCC.

    1. Motzer R, et al. Lenvatinib plus pembrolizumab or everolimus for advanced renal cell carcinoma. N Engl J Med. 2021;384(14):1289–1300.

      CLEAR trial demonstrated overall survival benefit of pembrolizumab/lenvatinib over sunitinib in advanced RCC.

Publication types

Supplementary concepts