Evidence map›Paper›PMID 39672382›Full record

Trial reportAnnals of oncology : official journal of the European Society for Medical Oncology2025

Biomarker analyses from the phase III randomized CLEAR trial: lenvatinib plus pembrolizumab versus sunitinib in advanced renal cell carcinoma.

R J Motzer, C Porta, M Eto, T E Hutson, S Y Rha, J R Merchan, E Winquist, H Gurney, V Grünwald, S George and 10 more

Abstract readRandomized Controlled TrialClinical Trial, Phase IIIComparative Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Annals of oncology : official journal of the European Society for Medical Oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed, 2 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

18 citing papers in PubMed, 2 syntheses or guidelines pooled it.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

20 authors.

R J MotzerMemorial Sloan Kettering Cancer Center, New York, USA. Electronic address: motzerr@mskcc.org.
C PortaInterdisciplinary Department of Medicine, University of Bari "A. Moro" and Division of Medical Oncology, Policlinico Consorziale di Bari, Bari, Italy.
M EtoDepartment of Urology, Kyushu University, Fukuoka, Japan.
T E HutsonTexas Tech University Health Science Center, Lubbock, USA.
S Y RhaYonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea.
J R MerchanUniversity of Miami Sylvester Comprehensive Cancer Center, Miami, USA.
E WinquistDepartment of Oncology, Western University, London, Ontario, Canada.
H GurneyDepartment of Medical Oncology, Macquarie University, Sydney, New South Wales, Australia.
V GrünwaldInterdisciplinary Genitourinary Oncology, Clinic for Urology, Clinic for Medical Oncology, University Hospital Essen, Essen, Germany.
S GeorgeRoswell Park Cancer Institute, Buffalo, USA.
J MarkensohnMerck & Co., Inc., Rahway, USA.
J E BurgentsMerck & Co., Inc., Rahway, USA.
R CristescuMerck & Co., Inc., Rahway, USA.
P SachdevEisai Inc., Nutley, USA.
Y NaritaEisai Co., Ltd., Ibaraki, Japan.
J HuangEisai Inc., Nutley, USA.
Z ZhaoEisai Inc., Nutley, USA.
C E OkparaEisai Ltd., Hatfield, UK.
Y MinoshimaEisai Co., Ltd., Ibaraki, Japan.
T K ChoueiriDana-Farber Cancer Institute, Boston, USA.

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4M
VectorP30CA006516 · NCI · DANA-FARBER CANCER INSTITUTE · PI JENNIFER W MACK · 1985 to 2026
$330.6M
Treating the P13-Kinase/AKTP50CA101942 · NCI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI David McDermott · 2003 to 2026
$53.4M
NCI NIH HHS P30 CA006516NCI NIH HHS P30 CA008748NCI NIH HHS P50 CA101942
6 · The paper itself

Abstract

backgroundIn CLEAR, lenvatinib + pembrolizumab (L + P) significantly improved efficacy versus sunitinib in first-line treatment of patients with advanced renal cell carcinoma (aRCC). We report results from CLEAR biomarker analyses. PATIENTS AND

methodsProgrammed death-ligand 1 (PD-L1) immunohistochemistry (IHC) and next-generation sequencing assays (whole exome sequencing/RNA sequencing) were carried out on archival tumor specimens. For IHC-derived/RNA sequencing analyses, a continuous analysis was carried out adjusting by Karnofsky performance status (KPS) score for: PD-L1 combined positive score (CPS) versus best overall response (BOR)/progression-free survival (PFS); and each gene signature score [T-cell inflamed gene expression profile (Tcell

resultsWithin-arm analyses using continuous values showed no association between PD-L1 levels and BOR/PFS for either treatment. PFS hazard ratios between arms were similar regardless of the mutant or wild-type subgroups of RCC driver genes (VHL, PBRM1, SETD2, BAP1, KDM5C). No associations between PFS and gene signature scores were observed for L + P. With sunitinib, high proliferation and MYC signature scores showed shorter PFS; high angiogenesis and microvessel density signature scores showed longer PFS. Six new molecular subtypes were defined. Tumors of patients with favorable/intermediate risk were enriched in angiogenesis and angiogenesis/stromal clusters; those with poor risk were enriched in proliferative and unclassified (low-Tcell

conclusionsImprovements in objective response rate and PFS for L + P versus sunitinib in aRCC were observed consistently across a range of biomarker subgroups defined using RCC driver mutations, PD-L1, gene expression signatures, and molecular subtypes.

Indexed as

Antineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorCarcinoma, Renal CellKidney NeoplasmsAdultAgedAntibodies, Monoclonal, HumanizedB7-H1 AntigenFemaleHumansMaleMiddle AgedPhenylurea CompoundsProgression-Free SurvivalQuinolinesSunitinibAntibodies, Monoclonal, HumanizedB7-H1 AntigenBiomarkers, TumorCD274 protein, humanlenvatinibpembrolizumabPhenylurea CompoundsQuinolinesSunitinibbiomarkersCLEARlenvatinibpembrolizumabRCC

Identifiers

PMID39672382
PMCPMC12459081

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.