PRISM: A randomised phase II trial of nivolumab in combination with alternatively scheduled ipilimumab in first-line treatment of patients with advanced or metastatic renal cell carcinoma

Collinson, Fiona; Brown, Sarah; Buckley, Hannah; Ainsworth, Gemma; Howard, Helen; Poad, Heather; Carr, Gregory J.; Banks, Roz; Brown, Julia; Velikova, Galina; Larkin, James; Nathan, Paul; Powles, Thomas; Vasudev, Naveen S.

doi:10.1093/annonc/mdy283.140

Cited by 2 publications

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“…The substantial improvement in OS obtained by combination treatments came with the price of increased toxicity that may not be suitable for real-life patients, who often have greater fragility and more comorbidities. Alternative regimens such as those used in the PRISM trial [ 75 ] and de-escalation strategies such as those used in the OMNIVORE or TITAN-RCC trials may address this issue, but more convincing data are needed to alter clinical practice. Another challenging issue is choosing among four first-line options that will never be compared together in a prospective trial.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Management of Metastatic Clear Cell Renal Cell Carcinoma: A Revolution in Every Decade

Larroquette

Lefort²,

Heraudet

et al. 2022

Cancers

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Clear cell renal cell carcinoma (RCC) oncogenesis is mainly driven by VHL gene inactivation, leading to overexpression of vascular endothelial growth factor (VEGF). The use of tyrosine-kinase inhibitors (TKIs) directed against VEGF and its receptor (VEGFR) revolutionised the management of metastatic renal cancer in the 2000s. The more recent development of next-generation TKIs such as cabozantinib or lenvatinib has made it possible to bypass some of the mechanisms of resistance to first-generation anti-VEGFR TKIs. During the decade 2010–2020, the development of immune checkpoint blockade (ICB) therapies revolutionised the management of many solid cancers, including RCC, in first- and subsequent-line settings. Dual ICB or ICB plus anti-VEGFR TKI combinations are now the standard of care for patients with advanced clear cell RCC. To optimise these combination therapies while preserving patient quality of life, escalation and de-escalation strategies are being evaluated in prospective randomised trials, based on patient selection according to their prognosis risk. Finally, new therapeutic approaches, such as targeting hypoxia-inducible factor (HIF) and the development of innovative treatments using antibody-drug conjugates (ADCs), CAR-T cells, or radiopharmaceuticals, are all potential candidates to improve further patient survival.

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Section: Discussionmentioning

confidence: 99%