학술논문

Impact of MET status on treatment outcomes in papillary renal cell carcinoma: A pooled analysis of historical data.
Document Type
Article
Source
European Journal of Cancer. Jul2022, Vol. 170, p158-168. 11p.
Subject
*RENAL cell carcinoma
*PAPILLARY carcinoma
*TREATMENT effectiveness
Language
ISSN
0959-8049
Abstract
Papillary renal cell carcinoma (PRCC) represents 15% of RCCs but has no indicated therapies, with limited biomarker-based data to inform targeted treatment. MET alterations may be key; > 80% of PRCC tumours show MET upregulation. The objective of this study was to assess MET status in PRCC and its impact on clinical outcomes. This retrospective, observational study included patients with locally advanced/metastatic PRCC from three international registries. MET status was determined retrospectively by next generation sequencing (NGS) of archival tissue. MET -driven was defined as MET and/or hepatocyte growth factor amplification, chromosome 7 gain, and/or MET kinase domain mutations. Objectives included progression-free survival (PFS) and overall survival (OS) by MET status using a Cox proportional hazards model. Of 308 patients, 305 received first-line treatment; most commonly sunitinib (n = 208; 68%), then everolimus (n = 40; 13%). Of 179 patients with valid NGS results, 38% had MET -driven and 49% MET -independent tumours (13% unevaluable). In the MET -driven versus MET -independent subgroups, respectively, of sunitinib-treated patients, median PFS was numerically longer, though not statistically significantly; PFS: 9.2 months (95% confidence interval [CI]: 5.4–13.2) versus 5.7 months (95% CI: 4.3–7.4), hazard ratio (HR) = 0.67; 95% CI: 0.41–1.08. There was no difference between the OS of each subgroup. MET -driven PRCC may respond to targeted agents. However, the presence of MET alterations did not appear to be predictive for outcomes in response to current therapies, which are not biomarker-driven, compared with MET -independent tumours. • This was a retrospective, observational, molecular epidemiology study. • Patients had locally advanced/metastatic PRCC that was MET-driven/MET-independent. • Patients with MET-driven tumours had numerically longer PFS and TTF versus MET-independent. • However, there was no difference in OS between the two groups. • MET-driven tumours may not predict poorer outcome versus MET-independent tumours. [ABSTRACT FROM AUTHOR]