Evidence map›Paper›PMID 35222506›Full record

ArticleLiver cancer2022

Outcomes Based on Plasma Biomarkers for the Phase 3 CELESTIAL Trial of Cabozantinib versus Placebo in Advanced Hepatocellular Carcinoma.

Lorenza Rimassa, Robin Kate Kelley, Tim Meyer, Baek-Yeol Ryoo, Philippe Merle, Joong-Won Park, Jean-Frederic Blanc, Ho Yeong Lim, Albert Tran, Yi-Wah Chan and 5 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Liver cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
2.3field-weighted citation impact, top 9% of its field
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

26 citing papers in PubMed, 32 citations in OpenAlex.

  1. Trial
  2. Review
  3. Targeting Tumor-Associated Macrophages and Cancer-Associated Fibroblasts to Overcome Therapeutic Resistance in Hepatocellular Carcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
    Review
  4. Review
  5. Review
  6. Article
  7. Review
  8. Review
  9. Review
  10. Article
  11. Article
  12. Article
  13. Review
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  16. Review
  17. Review
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  19. Article
  20. Cabozantinib for the treatment of solid tumors: a systematic review.Therapeutic advances in medical oncology · 2022
    Review
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

15 authors at 14 institutions in 6 countries.

Lorenza RimassaDepartment of Biomedical Sciences, Humanitas University, Pieve Emanuele (Milan), Italy.
Robin Kate KelleyUCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, California, USA.
Tim MeyerRoyal Free Hospital and UCL Cancer Institute, London, United Kingdom.
Baek-Yeol RyooAsan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Philippe MerleGroupement Hospitalier Lyon Nord, Lyon, France.
Joong-Won ParkNational Cancer Center, Goyang, Republic of Korea.
Jean-Frederic BlancHôpital Haut-Lévêque, CHU Bordeaux, Bordeaux, France.
Ho Yeong LimSamsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Albert TranUniversité Côte d'Azur, Nice, France.
Yi-Wah ChanFios Genomics Ltd, Edinburgh, United Kingdom.
Paul McAdamFios Genomics Ltd, Edinburgh, United Kingdom.
Evelyn WangExelixis, Inc., Alameda, California, USA.
Ann-Lii ChengNational Taiwan University College of Medicine, Taipei, Taiwan.
Anthony B El-KhoueiryUSC Norris Comprehensive Cancer Center, Los Angeles, California, USA.
Ghassan K Abou-AlfaMemorial Sloan Kettering Cancer Center, New York, New York, USA.
Fios Genomics (United Kingdom) · GBExelixis (United States) · USHôpital Cardiologique du Haut-Lévêque · FRHôpital Lyon Sud · FRHumanitas University · ITInserm · FRMemorial Sloan Kettering Cancer Center · USNational Cancer Center · KRNational Taiwan University · TWSamsung Medical Center · KRThe Royal Free Hospital · GBUCSF Helen Diller Family Comprehensive Cancer Center · USUlsan College · KRUSC Norris Comprehensive Cancer Center · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4M
Cancer Research UK 26813NCI NIH HHS P30 CA008748
6 · The paper itself

Abstract

introductionCabozantinib, an inhibitor of MET, AXL, and VEGF receptors, significantly improved overall survival (OS) and progression-free survival (PFS) versus placebo in patients with previously treated advanced hepatocellular carcinoma (HCC). In this exploratory analysis, outcomes were evaluated according to plasma biomarker levels.

methodsBaseline plasma levels were evaluated for MET, AXL, VEGFR2, HGF, GAS6, VEGF-A, PlGF, IL-8, EPO, ANG2, IGF-1, VEGF-C, and c-KIT for 674/707 randomized patients; and Week 4 levels were evaluated for MET, AXL, VEGFR2, HGF, GAS6, VEGF-A, PlGF, IL-8, and EPO for 614 patients. OS and PFS were analyzed by baseline levels as dichotomized or continuous variables and by on-treatment changes at Week 4 as continuous variables; biomarkers were considered potentially prognostic if

resultsIn the placebo group, high levels of MET, HGF, GAS6, IL-8, and ANG2 and low levels of IGF-1 were associated with shorter OS in univariate and multivariable analyses; these associations were also observed for MET, IL-8, and ANG2 in the cabozantinib group. Hazard ratios for OS and PFS favored cabozantinib over the placebo at low and high baseline levels for all biomarkers. No baseline biomarkers were predictive of a treatment benefit. Cabozantinib promoted pharmacodynamic changes in several biomarkers, including increases in VEGF-A, PlGF, AXL, and GAS6 levels and decreases in VEGFR2 and HGF levels; these changes were not associated with OS or PFS.

conclusionCabozantinib improved OS and PFS versus placebo at high and low baseline concentrations for all biomarkers analyzed. Low baseline levels of MET, HGF, GAS6, IL-8, and ANG2 and high levels of IGF-1 were identified as potential favorable prognostic biomarkers for survival in previously treated advanced HCC. Although cabozantinib promoted pharmacodynamic changes in several biomarkers, these changes were not associated with survival.

Indexed as

CabozantinibHepatocellular carcinomaPlasma biomarkersPrognostic factors

Identifiers

PMID35222506
PMCPMC8820164
OpenAlexW4200415204

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.