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Dual checkpoint-blockade in urothelial carcinoma—when is it so far

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Summary

Single agent immunotherapy is routinely used in the treatment of localised and advanced bladder cancer. Dual checkpoint inhibition with nivolumab (nivo)–ipilimumab (ipi) and durvalumab (durva)–tremelimumab (treme) shows encouraging activity in phase I/II trials in the neoadjuvant and metastatic disease setting. Several large trials are testing these combinations against the current standard of care. The so far reported results are negative; however, it appears that a subgroup of patients might profit substantially from dual checkpoint blockade. Ongoing trials will elucidate which patients will be candidates for this treatment modality in routine clinical care.

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References

  1. Grimm M‑O, Grün B, Niegisch G, Pichler M, Roghmann F, Schmitz-Dräger B, et al. Tailored immunotherapy approach with nivolumab in advanced transitional cell carcinoma (TITAN-TCC). J Clin Oncol. 2022;40(6_suppl):441–441.

    Article  Google Scholar 

  2. Sharma P, Siefker-Radtke AO, de Braud F, Basso U, Calvo E, Bono P, et al. Nivolumab (N) alone or in combination with ipilimumab (I) in patients (pts) with platinum-pretreated metastatic urothelial carcinoma (mUC): extended follow-up from CheckMate 032. Ann Oncol. 2020;31:S582–S3.

    Article  Google Scholar 

  3. Galsky MD, Powles T, Li S, Hennicken D, Sonpavde G. A phase 3, open-label, randomized study of nivolumab plus ipilimumab or standard of care (SOC) versus SOC alone in patients (pts) with previously untreated unresectable or metastatic urothelial carcinoma (mUC; CheckMate 901). J Clin Oncol. 2018;36(6_suppl):TPS539–TPS539.

    Article  Google Scholar 

  4. Powles T, van der Heijden MS, Castellano D, Galsky MD, Loriot Y, Petrylak DP, et al. Durvalumab alone and durvalumab plus tremelimumab versus chemotherapy in previously untreated patients with unresectable, locally advanced or metastatic urothelial carcinoma (DANUBE): a randomised, open-label, multicentre, phase 3 trial. Lancet Oncol. 2020;21(12):1574–88.

    Article  CAS  PubMed  Google Scholar 

  5. Galsky MD, Necchi A, Sridhar SS, Ogawa O, Angra N, Hois S, et al. A phase III, randomized, open-label, multicenter, global study of first-line durvalumab plus standard of care (SoC) chemotherapy and durvalumab plus tremelimumab, and SoC chemotherapy versus SoC chemotherapy alone in unresectable locally advanced or metastatic urothelial cancer (NILE). J Clin Oncol. 2021;39(6_suppl):TPS504–TPS504.

    Article  Google Scholar 

  6. van Dijk N, Gil-Jimenez A, Silina K, Hendricksen K, Smit LA, de Feijter JM, et al. Preoperative ipilimumab plus nivolumab in locoregionally advanced urothelial cancer: the NABUCCO trial. Nat Med. 2020;26(12):1839–44.

    Article  PubMed  Google Scholar 

  7. Gao J, Siefker-Radtke AO, Navai N, Campbell MT, Slack Tidwell R, Guo C, et al. A pilot presurgical study evaluating anti-PD-L1 durvalumab (durva) plus anti-CTLA‑4 tremelimumab (treme) in patients (pts) with high-risk muscle-invasive bladder carcinoma (MIBC) who are ineligible for cisplatin-based neoadjuvant chemotherapy (NAC). J Clin Oncol. 2019;37(15_suppl):4551–4551.

    Article  Google Scholar 

  8. Grande E, Guerrero F, Puente J, Galante I, Duran I, Dominguez M, et al. DUTRENEO Trial. A randomized phase II trial of DUrvalumab and TREmelimumab versus chemotherapy as a NEOadjuvant approach to muscle-invasive urothelial bladder cancer (MIBC) patients (pts) prospectively selected by an interferon (INF)-gamma immune signature. J Clin Oncol. 2020;38(15_suppl):5012–5012.

    Article  Google Scholar 

  9. Pfister C, Gravis G, Fléchon A, Chevreau C, Mahammedi H, Laguerre B, et al. Dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin or gemcitabine and cisplatin as perioperative chemotherapy for patients with nonmetastatic muscle-invasive bladder cancer: results of the GETUG-AFU V05 VESPER trial. J Clin Oncol. 2022;40(18):2013–22.

    Article  CAS  PubMed  Google Scholar 

  10. Bajorin DF, Witjes JA, Gschwend JE, Schenker M, Valderrama BP, Tomita Y, et al. Adjuvant nivolumab versus placebo in muscle-invasive urothelial carcinoma. N Engl J Med. 2021;384(22):2102–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Powles T, Drakaki A, Teoh JY‑C, Grande E, Fontes-Sousa M, Porta C, et al. A phase 3, randomized, open-label, multicenter, global study of the efficacy and safety of durvalumab (D) + tremelimumab (T) + enfortumab vedotin (EV) or D + EV for neoadjuvant treatment in cisplatin-ineligible muscle-invasive bladder cancer (MIBC) (VOLGA). J Clin Oncol. 2022;40(6_suppl):TPS579–TPS579.

    Article  Google Scholar 

  12. Garcia del Muro X, Valderrama BP, Medina A, Cuellar MA, Etxaniz O, Gironés Sarrió R, et al. Phase II trial of durvalumab plus tremelimumab with concurrent radiotherapy (RT) in patients (pts) with localized muscle invasive bladder cancer (MIBC) treated with a selective bladder preservation approach: Immunopreserve-Sogug trial. J Clin Oncol. 2021;39(15_suppl):4505–4505.

    Article  Google Scholar 

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Authors and Affiliations

  1. Department of Oncology, Hematology and Palliative Care, Clinic Ottakring, Vienna, Austria, Montlearstrasse 47, 1160

    Karl Mayrhofer MD & Dora Niedersüß-Beke MD, MBA

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  1. Karl Mayrhofer MD
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  2. Dora Niedersüß-Beke MD, MBA
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Correspondence to Karl Mayrhofer MD.

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K. Mayrhofer and D. Niedersüß-Beke declare that they have no competing interests.

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Mayrhofer, K., Niedersüß-Beke, D. Dual checkpoint-blockade in urothelial carcinoma—when is it so far. memo 16, 52–55 (2023). https://doi.org/10.1007/s12254-022-00839-0

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  • DOI: https://doi.org/10.1007/s12254-022-00839-0

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