{"doi":"10.1177/17562872211053189","title":"Is there a preferred first-line therapy for metastatic renal cell carcinoma? A network meta-analysis","abstract":"<jats:sec><jats:title>Background:</jats:title><jats:p> In recent years, new therapeutic combinations based on immunotherapy provided significant benefits as a first-line treatment for patients with advanced renal cell carcinoma (mRCC). </jats:p></jats:sec><jats:sec><jats:title>Objective:</jats:title><jats:p> This work aims to address the lack of head-to-head comparisons and the uncertainty of the benefit from immunotherapy-based combinations in all the International Metastatic RCC Database Consortium (IMDC) subgroups. </jats:p></jats:sec><jats:sec><jats:title>Design, setting, and participants:</jats:title><jats:p> A systematic review and a network meta-analysis were performed. Overall survival (OS) in the intention-to-treat (ITT) population was the primary endpoint. OS according to IMDC subgroups (favorable, intermediate, poor), PD-L1 expression, and grade ⩾3 adverse events (AEs) were secondary endpoints. A SUCRA analysis was performed. </jats:p></jats:sec><jats:sec><jats:title>Results and limitations:</jats:title><jats:p> Six randomized phase III trials with 5121 patients were included. There was a high likelihood (82%) that nivolumab-cabozantinib was the preferred treatment in OS. The benefit of ICI-based combinations over sunitinib was unclear in the favorable-risk subgroup. Nivolumab-ipilimumab had the best risk/benefit ratio among all the ICI-based combinations. The limitations were the lack of individual patient data; the heterogeneity of patients’ characteristics, trial designs, and follow-up times; and a limited number of studies for indirect comparisons. </jats:p></jats:sec><jats:sec><jats:title>Conclusions:</jats:title><jats:p> A customized approach for the first-line treatment of patients with mRCC should consider the risk/benefit profile of each treatment option, especially considering the likeliness of long-term survival finally reached in this setting. </jats:p></jats:sec>","journal":"Therapeutic Advances in Urology","year":2021,"id":630979,"datarank":0.4493598410330987,"base_score":2.995732273553991,"endowment":2.995732273553991,"self_citation_contribution":0.4493598410330987,"citation_network_contribution":0.0,"self_endowment_contribution":0.4493598410330987,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":19,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1580713,"name":"Carlo Messina","orcid":null,"position":1,"is_corresponding":false},{"id":1634938,"name":"Chiara Airoldi","orcid":null,"position":2,"is_corresponding":false},{"id":1028178,"name":"Sebastiano Buti","orcid":"0000-0003-0876-0226","position":3,"is_corresponding":false},{"id":1028182,"name":"Giandomenico Roviello","orcid":"0000-0001-5504-8237","position":4,"is_corresponding":false},{"id":1634939,"name":"Alessia Mennitto","orcid":null,"position":5,"is_corresponding":false},{"id":1027430,"name":"Orazio Caffo","orcid":null,"position":6,"is_corresponding":false},{"id":1142023,"name":"Alessandra Gennari","orcid":"0000-0002-0928-2281","position":7,"is_corresponding":false},{"id":800712,"name":"Melissa Bersanelli","orcid":"0000-0002-6527-6281","position":8,"is_corresponding":false},{"id":1634937,"name":"Carlo Cattrini","orcid":"0000-0003-4785-9480","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Is there a preferred first-line therapy for metastatic renal cell carcinoma? A network meta-analysis","abstract":"<jats:sec><jats:title>Background:</jats:title><jats:p> In recent years, new therapeutic combinations based on immunotherapy provided significant benefits as a first-line treatment for patients with advanced renal cell carcinoma (mRCC). </jats:p></jats:sec><jats:sec><jats:title>Objective:</jats:title><jats:p> This work aims to address the lack of head-to-head comparisons and the uncertainty of the benefit from immunotherapy-based combinations in all the International Metastatic RCC Database Consortium (IMDC) subgroups. </jats:p></jats:sec><jats:sec><jats:title>Design, setting, and participants:</jats:title><jats:p> A systematic review and a network meta-analysis were performed. Overall survival (OS) in the intention-to-treat (ITT) population was the primary endpoint. OS according to IMDC subgroups (favorable, intermediate, poor), PD-L1 expression, and grade ⩾3 adverse events (AEs) were secondary endpoints. A SUCRA analysis was performed. </jats:p></jats:sec><jats:sec><jats:title>Results and limitations:</jats:title><jats:p> Six randomized phase III trials with 5121 patients were included. There was a high likelihood (82%) that nivolumab-cabozantinib was the preferred treatment in OS. The benefit of ICI-based combinations over sunitinib was unclear in the favorable-risk subgroup. Nivolumab-ipilimumab had the best risk/benefit ratio among all the ICI-based combinations. The limitations were the lack of individual patient data; the heterogeneity of patients’ characteristics, trial designs, and follow-up times; and a limited number of studies for indirect comparisons. </jats:p></jats:sec><jats:sec><jats:title>Conclusions:</jats:title><jats:p> A customized approach for the first-line treatment of patients with mRCC should consider the risk/benefit profile of each treatment option, especially considering the likeliness of long-term survival finally reached in this setting. </jats:p></jats:sec>","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"34733356","pmcid":null,"openalex_id":null,"authors":[],"funders":[],"total_grants":0,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"gold","license":"cc-by-nc","oa_locations":[{"url":"https://journals.sagepub.com/doi/pdf/10.1177/17562872211053189","host_type":"publisher"},{"url":"https://journals.sagepub.com/doi/full-xml/10.1177/17562872211053189","host_type":"publisher"},{"url":"https://flore.unifi.it/bitstream/2158/1295685/2/cattrini-et-al-2021-is-there-a-preferred-first-line-therapy-for-metastatic-renal-cell-carcinoma-a-network-meta-analysis.pdf","host_type":"repository"},{"url":"https://doaj.org/article/7f88a95dc6f34403b9c22622b09df00e","host_type":"repository"},{"url":"http://europepmc.org/pmc/articles/PMC8558789","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/8558789","host_type":"repository"}],"fields_of_study":[],"mesh_terms":[],"keywords":["first-line","immune checkpoint inhibitors","meta-analysis","renal cell carcinoma","tyrosine kinase inhibitors"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-05T22:34:19.672445Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}