Combination treatments with immuno-oncology (IO) agents and IO agents plus a vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR-TKI) have been approved for first-line treatment of patients with metastatic renal cell carcinoma (mRCC).
No direct comparisons have been performed among these treatment options. We performed a systematic review and network meta-analysis to compare and rank the available regimens for first-line treatment in terms of survival benefit and efficacy. In accordance with the Preferred Reporting Items for Systematic Review statement, a systematic search of reported studies was performed in MEDLINE, the Cochrane Central Register of Controlled Trials, and EMBASE up to May 31, 2019. Network meta-analysis models were adjusted using the Bayesian method. Four randomized clinical trials, with a total of 3758 patients, met the inclusion criteria. Considering systemic therapy, 1880 patients had received sunitinib and 550, 432, 442, and 454 patients had received ipilimumab plus nivolumab (ipi + nivo), pembrolizumab plus axitinib (pembro + axi), avelumab plus axitinib (avelu + axi), and atezolizumab plus bevacizumab (atezo + bev). No difference was found in overall survival between ipi + nivo and pembro + axi for the intention to treat population (hazard ratio [HR], 1.34; 95% credible interval [CrI], 0.92-1.97). No difference was found in progression-free survival among the treatments. The overall response rate (ORR) was superior with pembro + axi and avelu + axi compared with the ORR with the other treatments (atezo + bev vs. pembro + axi: HR, 0.66; 95% CrI, 0.52-0.84; ipi + nivo vs. pembro + axi: HR, 0.73; 95% CrI, 0.59-0.90; atezo + bev vs. avelu + axi: HR, 0.55; 95% CrI, 0.43-0.71; avelu + axi vs. ipi + nivo: HR, 1.66; 95% CrI, 1.31-2.12), with no differences across them (HR, 1.21; 95% CrI, 0.95-1.53). In the present indirect comparison, for an intention to treat population, we found no survival differences between pembro + axi and ipi + nivo. All treatments showed better progression-free survival compared with sunitinib that was similar among them. The combination of an IO agent (pembrolizumab or avelumab) and axitinib seemed to be the most effective therapy for the ORR.
Clinical genitourinary cancer. 2020 Mar 04 [Epub ahead of print]
Fernando Sabino M Monteiro, Andrey Soares, Márcio Debiasi, Fabio A Schutz, Fernando Cotait Maluf, Diogo Assed Bastos, Andre Sasse, Carolina G S Cauduro, Gabriela Oliveira Mendes, Patricia K Ziegelmann, André P Fay
Latin American Cooperative Oncology Group, Genito-Urinary Tumors Section, Porto Alegre, Rio Grande do Sul, Brazil; Hospital Santa Lucia, Oncology and Hematology Department, Brasilia, Distrito Federal, Brazil; Hospital Universitário de Brasilia, Oncology Department, Brasília, Distrito Federal, Brazil; PUCRS, School of Medicine, Porto Alegre, Rio Grande do Sul, Brazil. Electronic address: ., Latin American Cooperative Oncology Group, Genito-Urinary Tumors Section, Porto Alegre, Rio Grande do Sul, Brazil; Grupo Oncoclínicas, Clinical Oncology Department, São Paulo, São Paulo, Brazil; Hospital Albert Einstein, Oncology Department, São Paulo, São Paulo, Brazil., Latin American Cooperative Oncology Group, Genito-Urinary Tumors Section, Porto Alegre, Rio Grande do Sul, Brazil., Latin American Cooperative Oncology Group, Genito-Urinary Tumors Section, Porto Alegre, Rio Grande do Sul, Brazil; BP - A Beneficência Portuguesa de São Paulo, Clinical Oncology Department, São Paulo, São Paulo, Brazil., Latin American Cooperative Oncology Group, Genito-Urinary Tumors Section, Porto Alegre, Rio Grande do Sul, Brazil; Hospital Albert Einstein, Oncology Department, São Paulo, São Paulo, Brazil; BP - A Beneficência Portuguesa de São Paulo, Clinical Oncology Department, São Paulo, São Paulo, Brazil., Latin American Cooperative Oncology Group, Genito-Urinary Tumors Section, Porto Alegre, Rio Grande do Sul, Brazil; Hospital Sirio-Libanes, Clinical Oncology Department, São Paulo, São Paulo, Brazil., Latin American Cooperative Oncology Group, Genito-Urinary Tumors Section, Porto Alegre, Rio Grande do Sul, Brazil; Grupo Sonhe, Clinical Oncology Department, Campinas, São Paulo, Brazil., Université Libre de Bruvelles, Medicine Department, Brussels, Belgium., Hospital Santa Lucia, Oncology and Hematology Department, Brasilia, Distrito Federal, Brazil., Universidade Federal do Rio Grande do Sul, Epidemiology Post Graduation Program, Porto Alegre, Rio Grande do Sul, Brazil., Latin American Cooperative Oncology Group, Genito-Urinary Tumors Section, Porto Alegre, Rio Grande do Sul, Brazil; PUCRS, School of Medicine, Porto Alegre, Rio Grande do Sul, Brazil; Grupo Oncoclínicas, Clinical Oncology Department, São Paulo, São Paulo, Brazil; Hospital São Lucas da PUCRS, Oncology Department, Porto Alegre, Rio Grande do Sul, Brazil.
PubMed http://www.ncbi.nlm.nih.gov/pubmed/32303427