Mesenchymal-Epithelial Transition Kinase Inhibitor Therapy in Patients with Advanced Papillary Renal-Cell Carcinoma: A Systematic Review and Meta-Analysis.

Papillary subtypes of renal-cell carcinoma (pRCC) represent 10-15% of the cases and commonly have MET alterations. This systematic review and single-arm meta-analysis evaluated MET inhibitor therapy (METi) efficacy and safety in adults with confirmed advanced pRCC. The search strategy included PubMed, Web-of-science, Cochrane, and Scopus. We used the DerSimonian/Laird random effect model for all analyses; p-value < 5% was considered significant, and heterogeneity was assessed with I2. Three clinical trials and six cohort studies were included with 504 patients; 31% were MET-driven. Our pooled analysis demonstrated an objective response rate (ORR) in MET-driven, MET-independent, and overall patients of: 36% (95%CI: 10-62), 0% (95%CI: 0-3), and 21% (95%CI: 1-41), respectively. One-year disease control and progression-free survival rates were, respectively, 70% (95%CI: 52-88) and 15% (95%CI: 10-20). Twelve- and twenty-four-month survival rates were, respectively, 43% (95%CI: 23-64) and 10% (95%CI: 0-30). The prevalence of adverse events of any grade and grades 3-5 were 96% (95%CI: 91-100) and 44% (95%CI: 37-50), respectively. We suggest METi has anti-tumor activity and is tolerable in patients with advanced pRCC.

International journal of molecular sciences. 2023 Dec 18*** epublish ***

Francisco Cezar Aquino de Moraes, Maysa Vilbert, Vinícius Freire Costa Alves, Gustavo de Oliveira Almeida, Jonathan N Priantti, Thiago Madeira, Carlos Stecca, Marianne Rodrigues Fernandes, Ney Pereira Carneiro Dos Santos

Oncology Research Center, Federal University of Pará, Belem 66075-110, Brazil., Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5T 2S8, Canada., School of Medicine, University of São Paulo-USP, São Paulo 14040-904, Brazil., School of Medicine, Federal University of Triângulo Mineiro-UFTM, Uberaba 38280-000, Brazil., School of Medicine, Federal University of Amazonas-UFAM, Manaus 69020-160, Brazil., School of Medicine, Federal University of Minas Gerais-UFMG, Belo Horizonte 31270-901, Brazil., Mackenzie Evangelical University Hospital, Curitiba 80710-390, Brazil.