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Kidney cancer

A triple dose of optimism: an initial foray into triplet therapy in metastatic renal cell carcinoma

COSMIC-313 combines all of the approved drugs against actionable targets in renal cell carcinoma into one triplet regimen. Although this approach has greater clinical efficacy than one of the standard-of-care doublet therapies, toxicities can limit adequate drug administration and, thus, we argue that this regimen should not yet be adopted. We also discuss ongoing investigations of other triplet regimens.

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References

  1. 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  PubMed  PubMed Central  Google Scholar 

  2. Rini, B. I. et al. Pembrolizumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N. Engl. J. Med. 380, 1116–1127 (2019).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  4. Williams, S. D., Loehrer, P. J., Nichols, C. R. & Einhorn, L. N. Chemotherapy of male and female germ cell tumors. Semin. Oncol. 19(Suppl 5), 19–23 (1992). discussion 23–24.

    CAS  PubMed  Google Scholar 

  5. Choueiri, T. K. et al. Cabozantinib plus nivolumab and ipilimumab in renal-cell carcinoma. N. Engl. J. Med. 388, 1767–1778 (2023).

    Article  CAS  PubMed  Google Scholar 

  6. Apolo, A. B. et al. Phase I study of cabozantinib and nivolumab alone or with ipilimumab for advanced or metastatic urothelial carcinoma and other genitourinary tumors. J. Clin. Oncol. 38, 3672–3684 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Apolo, A. B. et al. Nivolumab plus ipilimumab plus cabozantinib triplet combination for patients with previously untreated advanced renal cell carcinoma: results from a discontinued arm of the phase III CheckMate 9ER trial. Eur. J. Cancer 177, 63–71 (2022).

    Article  CAS  PubMed  Google Scholar 

  8. Motzer, R. J. et al. Nivolumab plus cabozantinib versus sunitinib in first-line treatment for advanced renal cell carcinoma (CheckMate 9ER): long-term follow-up results from an open-label, randomised, phase 3 trial. Lancet Oncol. 23, 888–898 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Vano, Y. A. et al. Nivolumab, nivolumab-ipilimumab, and VEGFR-tyrosine kinase inhibitors as first-line treatment for metastatic clear-cell renal cell carcinoma (BIONIKK): a biomarker-driven, open-label, non-comparative, randomised, phase 2 trial. Lancet Oncol. 23, 612–624 (2022).

    Article  CAS  PubMed  Google Scholar 

  10. Chen, Y.-W. et al. Optimal treatment by invoking biologic clusters in renal cell carcinoma (OPTIC RCC). J. Clin. Oncol. 41, TPS742 (2023).

    Article  Google Scholar 

Download references

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Correspondence to Brian I. Rini.

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K.E.B. has received institutional research funding from BMS, Eisai, Exelixis, Pfizer and Merck. K.E.B. has acted as a consultant for BMS and Exelixis. B.I.R. has received institutional research funding and/or has acted as a consultant for BMS, Eisai, Exelixis, Pfizer and Merck.

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Beckermann, K.E., Rini, B.I. A triple dose of optimism: an initial foray into triplet therapy in metastatic renal cell carcinoma. Nat Rev Clin Oncol 20, 581–582 (2023). https://doi.org/10.1038/s41571-023-00795-6

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