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• W4283777508 abstract "In their letter related to our BIONIKK II trial, 1 Vano Y-A Elaidi R Bennamoun M 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. 2022; 23: 612-624 Summary Full Text Full Text PDF PubMed Scopus (9) Google Scholar Burcu Ulaş Kahya and colleagues addressed the relevant issue of the heterogeneity of primary and metastatic tumours. Kahya and colleagues discuss that this heterogeneity is a challenge that could hinder the standardisation of molecular-based biomarker discovery. In addition to the relevant publications cited by the authors, Serie and colleagues 2 Serie DJ Joseph RW Cheville JC et al. Clear cell type A and B molecular subtypes in metastatic clear cell renal cell carcinoma: tumor heterogeneity and aggressiveness. Eur Urol. 2017; 71: 979-985 Summary Full Text Full Text PDF PubMed Scopus (44) Google Scholar reported 43% (35 of 81 patients) discordance in the gene expression signatures of ClearCode34, clear-cell type A (ccA)and clear-cell type B (ccB), between primary and metastatic tissues. 28 (80%) of the 35 patients with genetic discordance had a switch from the favourable prognosis group (ccA) in the primary tumour to the unfavourable prognosis group (ccB) in the metastatic tissue. Roussel and colleagues 3 Roussel E Kinget L Verbiest A et al. Molecular heterogeneity between paired primary and metastatic lesions from clear cell renal cell carcinoma. Eur Urol Open Sci. 2022; 40: 54-57 Summary Full Text Full Text PDF PubMed Scopus (1) Google Scholar also reported a 42% (26 of 62 patients) discordance of clear-cell renal cell carcinoma molecular groups between primary and metastatic (resected) pairs in patients with metastatic renal cell carcinoma. The authors observed that 18 (69%) of the 26 patients with discordant molecular groups had a switch from the favourable prognosis groups (ccrcc2 and ccrcc3) in the primary tissue to the unfavourable prognosis groups (ccrcc1 and ccrcc4) in the metastases or metastatic tissue. 3 Roussel E Kinget L Verbiest A et al. Molecular heterogeneity between paired primary and metastatic lesions from clear cell renal cell carcinoma. Eur Urol Open Sci. 2022; 40: 54-57 Summary Full Text Full Text PDF PubMed Scopus (1) Google Scholar The authors of both studies considered molecular grouping of metastatic lesions as the preferred method for capturing the maximum aggressiveness of the disease. 2 Serie DJ Joseph RW Cheville JC et al. Clear cell type A and B molecular subtypes in metastatic clear cell renal cell carcinoma: tumor heterogeneity and aggressiveness. Eur Urol. 2017; 71: 979-985 Summary Full Text Full Text PDF PubMed Scopus (44) Google Scholar , 3 Roussel E Kinget L Verbiest A et al. Molecular heterogeneity between paired primary and metastatic lesions from clear cell renal cell carcinoma. Eur Urol Open Sci. 2022; 40: 54-57 Summary Full Text Full Text PDF PubMed Scopus (1) Google Scholar Thus, we did not want to exclude metastatic sites from molecular grouping in the BIONIKK study. 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 trialWe demonstrate the feasibility and positive effect of a prospective patient selection based on tumour molecular phenotype to choose the most efficacious treatment between nivolumab with or without ipilimumab and a VEGFR-TKI in the first-line treatment of metastatic clear-cell renal cell carcinoma. Full-Text PDF How molecularly similar are primary and metastatic tissues in renal cell carcinoma?We read the BIONIKK study by Yann-Alexandre Vano and colleagues.1 Improved survival was achieved with immunotherapies and tyrosine-kinase inhibitors in metastatic clear-cell renal cell carcinoma. This study showed that treatment choice, according to the molecular subtype, is feasible. However, we have a few concerns about the methods used in the study. Full-Text PDF" @default.
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• W4283777508 date "2022-07-01" @default.
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• W4283777508 title "How molecularly similar are primary and metastatic tissues in renal cell carcinoma? – Authors’ reply" @default.
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• W4283777508 doi "https://doi.org/10.1016/s1470-2045(22)00344-8" @default.
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