Pembrolizumab plus axitinib versus sunitinib for advanced clear cell renal cell carcinoma: 5-year survival and biomarker analyses of the phase 3 KEYNOTE-426 trial

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15110%2F25%3A73635358" target="_blank" >RIV/61989592:15110/25:73635358 - isvavai.cz</a>

Result on the web

<a href="https://www.nature.com/articles/s41591-025-03867-5" target="_blank" >https://www.nature.com/articles/s41591-025-03867-5</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41591-025-03867-5" target="_blank" >10.1038/s41591-025-03867-5</a>

Result language

angličtina

Original language name

Pembrolizumab plus axitinib versus sunitinib for advanced clear cell renal cell carcinoma: 5-year survival and biomarker analyses of the phase 3 KEYNOTE-426 trial

Original language description

At the first interim analysis of the phase 3 KEYNOTE-426 trial, first-line pembrolizumab plus axitinib showed superior overall survival (OS), progression-free survival (PFS) and objective response rate (ORR) over sunitinib for advanced renal cell carcinoma (RCC). To assess long-term durability of clinical outcomes and elucidate predictive biomarkers for RCC, we performed efficacy and prespecified exploratory biomarker analyses from KEYNOTE-426 with ≥5 years of follow-up. Pembrolizumab plus axitinib showed sustained benefits in OS (hazard ratio: 0.84; 95% confidence interval: 0.71–0.99), PFS (hazard ratio: 0.69; 95% confidence interval: 0.59–0.81) and ORR (60.6% versus 39.6%) compared to sunitinib. An 18-gene T-cell-inflamed gene expression profile (Tcell&lt;inf&gt;inf&lt;/inf&gt;GEP) was positively associated with OS (P = 0.002), PFS (P &lt; 0.0001) and ORR (P &lt; 0.0001) within the pembrolizumab plus axitinib arm. An angiogenesis signature was positively associated with OS (P = 0.004) within the pembrolizumab plus axitinib arm and with OS (P &lt; 0.0001), PFS (P &lt; 0.001) and ORR (P = 0.002) within the sunitinib arm. Across arms, programmed cell death ligand 1 combined positive score was only associated (negatively) with OS within the sunitinib arm (P = 0.025). Additionally, PBRM1 (polybromo-1) mutation had a positive association with ORR (P = 0.002) within the pembrolizumab plus axitinib arm. Within the sunitinib arm, OS was positively associated with VHL (von Hippel–Lindau tumor suppressor gene) (P = 0.040) and PBRM1 (P = 0.010) mutations and was negatively associated with BAP1 (BRCA1-associated protein 1) mutation (P = 0.019). Results showed a sustained clinical benefit with pembrolizumab plus axitinib over sunitinib and provide valuable information on biomarkers for immunotherapy-based treatment combinations in advanced RCC. Prospective clinical investigations are needed for biomarker-directed treatment for advanced RCC. ClinicalTrials.gov identifier: NCT02853331.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30204 - Oncology

Project

—

Continuities

N - Vyzkumna aktivita podporovana z neverejnych zdroju

Publication year

2025

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

NATURE MEDICINE

ISSN

—

e-ISSN

1546-170X

Volume of the periodical

31

Issue of the periodical within the volume

August

Country of publishing house

US - UNITED STATES

Number of pages

10

Pages from-to

"3475–3484"

UT code for WoS article

001542530200001

EID of the result in the Scopus database

2-s2.0-105012404675