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

• Published in: International journal of molecular sciences Vol. 24; no. 24; p. 17582
• Main Authors: Moraes, Francisco Cezar Aquino de, Vilbert, Maysa, Alves, Vinícius Freire Costa, de Oliveira Almeida, Gustavo, Priantti, Jonathan N, Madeira, Thiago, Stecca, Carlos, Fernandes, Marianne Rodrigues, Dos Santos, Ney Pereira Carneiro
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 18.12.2023
• Subjects: Adult; advanced papillary renal-cell carcinoma; Bias; Cancer; Carcinoma, Renal Cell - drug therapy; Carcinoma, Renal Cell - pathology; Cell cycle; Chromosomes; Citation management software; Clinical trials; Cohort Studies; Disease control; Enzyme Therapy; Gene amplification; Histology; Humans; Kidney cancer; Kidney Neoplasms - pathology; Kinases; Medical research; MET inhibitors; MET status; Meta-analysis; Metastasis; Oncology; Protein Kinase Inhibitors - adverse effects; Response rates; Tumors; Vascular endothelial growth factor; United States > US; MET inhibitors; MET status; advanced papillary renal-cell carcinoma
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms242417582

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; -value < 5% was considered significant, and heterogeneity was assessed with I . 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.