Evidence map›Paper›PMID 41115467›Full record

Trial reportAnnals of oncology : official journal of the European Society for Medical Oncology2026

A multicenter randomized phase II trial of lenvatinib plus everolimus versus cabozantinib in patients with metastatic clear-cell RCC that progressed on PD-1 immune checkpoint inhibition (LenCabo).

A W Hahn, J Chahoud, W P Skelton, Y Yuan, A J Zurita-Saavedra, C Kovitz, O Alhalabi, M T Campbell, E Jonasch, J K Lin and 6 more

Abstract readRandomized Controlled TrialClinical Trial, Phase IIMulticenter 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, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed, 1 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

9 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Article
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  5. Article
  6. Article
  7. Review
  8. Review
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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

16 authors.

A W HahnDepartment of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA. Electronic address: ahahn@mdanderson.org.
J ChahoudDepartment of Genitourinary Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, USA.
W P SkeltonDivision of Hematology and Oncology, University of Virginia, Charlottesville, USA.
Y YuanDepartment of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, USA.
A J Zurita-SaavedraDepartment of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.
C KovitzDepartment of General Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.
O AlhalabiDepartment of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.
M T CampbellDepartment of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.
E JonaschDepartment of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.
J K LinDepartment of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.
M DesaiDepartment of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.
M J M N SantosDepartment of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.
H HwangDepartment of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, USA.
P G CornDepartment of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.
P MsaouelDepartment of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA; Department of David H. Koch Center for Applied Research of Genitourinary Cancers, The University of Texas, MD Anderson Cancer Center, Houston, USA; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, USA; The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences (GSBS), Houston, USA. Electronic address: pmsaouel@mdanderson.org.
N M TannirDepartment of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA. Electronic address: ntannir@mdanderson.org.

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8M
Elucidating T Cell Ferroptosis in Renal Medullary Carcinoma: 3D Genome Architecture Rewiring and Therapeutic AlleviationR01CA285454 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Wenbo Li, Pavlos Msaouel · 2024 to 2026
$2.0M
Mechanisms of Hyperprogression to Immunotherapy in SMARCB1-Deficient Renal MalignanciesR37CA288448 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Pavlos Msaouel · 2024 to 2026
$2.0M
NCI NIH HHS P30 CA016672NCI NIH HHS R01 CA285454NCI NIH HHS R37 CA288448
6 · The paper itself

Abstract

backgroundFirst-line treatments for metastatic clear-cell renal-cell carcinoma (ccRCC) combine programmed cell death protein 1 (PD-1) immune checkpoint inhibition (ICI) with cytotoxic T-lymphocyte associated protein 4 ICI or angiogenesis targeted therapies (TT). Upon progression, common options include cabozantinib or lenvatinib + everolimus, although these regimens have never been directly compared. We hypothesized that lenvatinib + everolimus will improve progression-free survival (PFS) compared with cabozantinib after progression on PD-1 ICI. PATIENTS AND

methodsThis multicenter, randomized phase II trial enrolled patients with metastatic ccRCC previously treated with one to two lines including PD-1 ICI. Participants received lenvatinib 18 mg/day + everolimus 5 mg/day versus cabozantinib 60 mg/day, stratified by International Metastatic RCC Database Consortium risk group and prior TT. A Bayesian optimal phase II design was used.

resultsIn total 90 patients were randomized; 86 patients received at least one dose of assigned lenvatinib + everolimus (n = 40) or cabozantinib (n = 46). Median time from randomization to data cut-off date (1 August 2025) was 20 months (interquartile range 14.9-22.5 months). A total of 60 PFS events were observed. Median PFS was 15.7 months with lenvatinib + everolimus and 10.2 months with cabozantinib [hazard ratio 0.51, 95% confidence interval (CI) 0.29-0.89, P = 0.02]. The objective response rate was 52.6% with lenvatinib + everolimus and 38.6% with cabozantinib. Overall survival (OS) data were immature and inconclusive due to a low number of events (n = 24/86; 1-year OS probability 87.0% versus 84.6% [95% CI 0.47% to 2.38%] with lenvatinib + everolimus versus cabozantinib, respectively. Discontinuation rates due to toxicity were 20% with lenvatinib + everolimus and 10.9% with cabozantinib.

conclusionsIn this randomized phase II trial in metastatic ccRCC that progressed on prior PD-1 ICIs, lenvatinib + everolimus significantly prolonged PFS over cabozantinib. As the first head-to-head comparison of contemporary second-line or later treatments after ICI, these results are relevant to treatment sequencing and inform oncology practice.

Indexed as

AnilidesAntineoplastic Combined Chemotherapy ProtocolsCarcinoma, Renal CellEverolimusImmune Checkpoint InhibitorsKidney NeoplasmsPhenylurea CompoundsAdultAgedAged, 80 and overFemaleHumansMaleMiddle AgedProgrammed Cell Death 1 ReceptorProgression-Free SurvivalAnilidescabozantinibEverolimusImmune Checkpoint InhibitorslenvatinibPDCD1 protein, humanPhenylurea CompoundsProgrammed Cell Death 1 ReceptorPyridinesQuinolinescabozantinibclear celleverolimuslenvatinibmetastatic renal-cell carcinomasalvagesecond-line

Identifiers

PMID41115467
PMCPMC12641504

What OpenQuestion holds

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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.