Impact of MET status on treatment outcomes in papillary renal cell carcinoma: A pooled analysis of historical data.
Biomarkers
Clinical-stage research
Drug targets
Genitourinary cancers
MET
PRCC
Sunitinib
Journal
European journal of cancer (Oxford, England : 1990)
ISSN: 1879-0852
Titre abrégé: Eur J Cancer
Pays: England
ID NLM: 9005373
Informations de publication
Date de publication:
07 2022
07 2022
Historique:
received:
24
03
2022
accepted:
14
04
2022
pubmed:
1
6
2022
medline:
29
6
2022
entrez:
31
5
2022
Statut:
ppublish
Résumé
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.
Sections du résumé
BACKGROUND
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.
METHODS
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.
RESULTS
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.
CONCLUSIONS
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.
Identifiants
pubmed: 35640484
pii: S0959-8049(22)00231-3
doi: 10.1016/j.ejca.2022.04.021
pii:
doi:
Substances chimiques
Sunitinib
V99T50803M
Types de publication
Journal Article
Meta-Analysis
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
158-168Informations de copyright
Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.