Evidence map›Paper›PMID 34818478›Full record

Trial reportThe New England journal of medicine2021

Belzutifan for Renal Cell Carcinoma in von Hippel-Lindau Disease.

Eric Jonasch, Frede Donskov, Othon Iliopoulos, W Kimryn Rathmell, Vivek K Narayan, Benjamin L Maughan, Stephane Oudard, Tobias Else, Jodi K Maranchie, Sarah J Welsh and 6 more

3 registry-linked trialsOpen access · bronzeAbstract readClinical Trial, Phase II
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The New England journal of medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 413 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
413citing papers in PubMed, 2 pooled it
36.0field-weighted citation impact, top 1% 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.

NCT03401788 phase2active not recruitingnot on this map

An Open-Label Phase 2 Study to Evaluate PT2977 for the Treatment of Von Hippel Lindau Disease-Associated Renal Cell Carcinoma

TypeinterventionalSponsorPeloton Therapeutics, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)Ran2018 to 2027Enrolled50ConditionsVHL - Von Hippel-Lindau Syndrome, VHL Gene Mutation, VHL Syndrome, VHL Gene InactivationArmsBelzutifan
NCT07167329 phase2recruitingnot on this mapstarted 2024, after this paper: background citation

The BELIEVE-VHL Trial: A Real-world Longitudinal Study on Belzutifan's Effectiveness, Pharmacogenetics, and Pharmacoeconomics in Von Hippel-Lindau (VHL) Syndrome Using the HIF2α Inhibitor Belzutifan

TypeinterventionalSponsorJosé Claudio Casali da RochaRan2024 to 2030Enrolled100ConditionsVon Hippel Lindau, Von Hippel Lindau Disease, Von Hippel Lindau-Deficient Clear Cell Renal Cell Carcinoma, Hemangioblastoma (HB) of the Central Nervous System (CNS)ArmsBelzutifan
NCT07554508 not yet recruitingnot on this mapstarted 2026, after this paper: background citation

A Prospective Registry for Belzutifan in the Treatment of Von Hippel-Lindau (VHL) Disease

TypeobservationalSponsorChinese University of Hong KongRan2026 to 2029Enrolled100ConditionsVHL - Von Hippel-Lindau Syndrome
3 · Its place in the literature

Who cites it

413 citing papers in PubMed, 2 syntheses or guidelines pooled it, 612 citations in OpenAlex.

  1. Guideline
  2. Pooled it
  3. Trial
  4. Trial
  5. Randomized phase II dose comparison LITESPARK-013 study of belzutifan in patients with advanced clear cell renal cell carcinoma.Annals of oncology : official journal of the European Society for Medical Oncology · 2024
    Trial
  6. Trial
  7. Niches in cancer: from primary tumors to metastatic disease.Journal of hematology & oncology · 2026
    Review
  8. [Belzutifan in the treatment of renal cell carcinoma].Urologie (Heidelberg, Germany) · 2026
    Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Review
  14. Review
  15. Rare solid tumours as indicators of hereditary cancer syndromes.European journal of human genetics : EJHG · 2026
    Review
  16. [Hereditary neuroendocrine neoplasms].Pathologie (Heidelberg, Germany) · 2026
    Review
  17. Review
  18. Review
  19. Article
  20. Review

353 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors at 1 institution in 1 country.

Eric JonaschFrom the University of Texas M.D. Anderson Cancer Center, Houston (E.J.); Aarhus University Hospital, Aarhus, Denmark (F.D.); Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston (O.I.); Vanderbilt University Medical Center, Nashville (W.K.R.); University of Pennsylvania, Philadelphia (V.K.N.); the University of Utah, Salt Lake City (B.L.M.); Hôpital Européen Georges-Pompidou, University of Paris, Paris (S.O.); the University of Michigan, Ann Arbor (T.E.); the University of Pittsburgh, Pittsburgh (J.K.M.); Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom (S.J.W.); Merck, Kenilworth, NJ (S.T., E.K.P., R.F.P.); and the Center for Cancer Research, National Cancer Institute, Bethesda, MD (W.M.L., R.S.).
Frede DonskovFrom the University of Texas M.D. Anderson Cancer Center, Houston (E.J.); Aarhus University Hospital, Aarhus, Denmark (F.D.); Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston (O.I.); Vanderbilt University Medical Center, Nashville (W.K.R.); University of Pennsylvania, Philadelphia (V.K.N.); the University of Utah, Salt Lake City (B.L.M.); Hôpital Européen Georges-Pompidou, University of Paris, Paris (S.O.); the University of Michigan, Ann Arbor (T.E.); the University of Pittsburgh, Pittsburgh (J.K.M.); Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom (S.J.W.); Merck, Kenilworth, NJ (S.T., E.K.P., R.F.P.); and the Center for Cancer Research, National Cancer Institute, Bethesda, MD (W.M.L., R.S.).
Othon IliopoulosFrom the University of Texas M.D. Anderson Cancer Center, Houston (E.J.); Aarhus University Hospital, Aarhus, Denmark (F.D.); Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston (O.I.); Vanderbilt University Medical Center, Nashville (W.K.R.); University of Pennsylvania, Philadelphia (V.K.N.); the University of Utah, Salt Lake City (B.L.M.); Hôpital Européen Georges-Pompidou, University of Paris, Paris (S.O.); the University of Michigan, Ann Arbor (T.E.); the University of Pittsburgh, Pittsburgh (J.K.M.); Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom (S.J.W.); Merck, Kenilworth, NJ (S.T., E.K.P., R.F.P.); and the Center for Cancer Research, National Cancer Institute, Bethesda, MD (W.M.L., R.S.).
W Kimryn RathmellFrom the University of Texas M.D. Anderson Cancer Center, Houston (E.J.); Aarhus University Hospital, Aarhus, Denmark (F.D.); Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston (O.I.); Vanderbilt University Medical Center, Nashville (W.K.R.); University of Pennsylvania, Philadelphia (V.K.N.); the University of Utah, Salt Lake City (B.L.M.); Hôpital Européen Georges-Pompidou, University of Paris, Paris (S.O.); the University of Michigan, Ann Arbor (T.E.); the University of Pittsburgh, Pittsburgh (J.K.M.); Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom (S.J.W.); Merck, Kenilworth, NJ (S.T., E.K.P., R.F.P.); and the Center for Cancer Research, National Cancer Institute, Bethesda, MD (W.M.L., R.S.).
Vivek K NarayanFrom the University of Texas M.D. Anderson Cancer Center, Houston (E.J.); Aarhus University Hospital, Aarhus, Denmark (F.D.); Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston (O.I.); Vanderbilt University Medical Center, Nashville (W.K.R.); University of Pennsylvania, Philadelphia (V.K.N.); the University of Utah, Salt Lake City (B.L.M.); Hôpital Européen Georges-Pompidou, University of Paris, Paris (S.O.); the University of Michigan, Ann Arbor (T.E.); the University of Pittsburgh, Pittsburgh (J.K.M.); Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom (S.J.W.); Merck, Kenilworth, NJ (S.T., E.K.P., R.F.P.); and the Center for Cancer Research, National Cancer Institute, Bethesda, MD (W.M.L., R.S.).
Benjamin L MaughanFrom the University of Texas M.D. Anderson Cancer Center, Houston (E.J.); Aarhus University Hospital, Aarhus, Denmark (F.D.); Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston (O.I.); Vanderbilt University Medical Center, Nashville (W.K.R.); University of Pennsylvania, Philadelphia (V.K.N.); the University of Utah, Salt Lake City (B.L.M.); Hôpital Européen Georges-Pompidou, University of Paris, Paris (S.O.); the University of Michigan, Ann Arbor (T.E.); the University of Pittsburgh, Pittsburgh (J.K.M.); Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom (S.J.W.); Merck, Kenilworth, NJ (S.T., E.K.P., R.F.P.); and the Center for Cancer Research, National Cancer Institute, Bethesda, MD (W.M.L., R.S.).
Stephane OudardFrom the University of Texas M.D. Anderson Cancer Center, Houston (E.J.); Aarhus University Hospital, Aarhus, Denmark (F.D.); Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston (O.I.); Vanderbilt University Medical Center, Nashville (W.K.R.); University of Pennsylvania, Philadelphia (V.K.N.); the University of Utah, Salt Lake City (B.L.M.); Hôpital Européen Georges-Pompidou, University of Paris, Paris (S.O.); the University of Michigan, Ann Arbor (T.E.); the University of Pittsburgh, Pittsburgh (J.K.M.); Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom (S.J.W.); Merck, Kenilworth, NJ (S.T., E.K.P., R.F.P.); and the Center for Cancer Research, National Cancer Institute, Bethesda, MD (W.M.L., R.S.).
Tobias ElseFrom the University of Texas M.D. Anderson Cancer Center, Houston (E.J.); Aarhus University Hospital, Aarhus, Denmark (F.D.); Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston (O.I.); Vanderbilt University Medical Center, Nashville (W.K.R.); University of Pennsylvania, Philadelphia (V.K.N.); the University of Utah, Salt Lake City (B.L.M.); Hôpital Européen Georges-Pompidou, University of Paris, Paris (S.O.); the University of Michigan, Ann Arbor (T.E.); the University of Pittsburgh, Pittsburgh (J.K.M.); Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom (S.J.W.); Merck, Kenilworth, NJ (S.T., E.K.P., R.F.P.); and the Center for Cancer Research, National Cancer Institute, Bethesda, MD (W.M.L., R.S.).
Jodi K MaranchieFrom the University of Texas M.D. Anderson Cancer Center, Houston (E.J.); Aarhus University Hospital, Aarhus, Denmark (F.D.); Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston (O.I.); Vanderbilt University Medical Center, Nashville (W.K.R.); University of Pennsylvania, Philadelphia (V.K.N.); the University of Utah, Salt Lake City (B.L.M.); Hôpital Européen Georges-Pompidou, University of Paris, Paris (S.O.); the University of Michigan, Ann Arbor (T.E.); the University of Pittsburgh, Pittsburgh (J.K.M.); Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom (S.J.W.); Merck, Kenilworth, NJ (S.T., E.K.P., R.F.P.); and the Center for Cancer Research, National Cancer Institute, Bethesda, MD (W.M.L., R.S.).
Sarah J WelshFrom the University of Texas M.D. Anderson Cancer Center, Houston (E.J.); Aarhus University Hospital, Aarhus, Denmark (F.D.); Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston (O.I.); Vanderbilt University Medical Center, Nashville (W.K.R.); University of Pennsylvania, Philadelphia (V.K.N.); the University of Utah, Salt Lake City (B.L.M.); Hôpital Européen Georges-Pompidou, University of Paris, Paris (S.O.); the University of Michigan, Ann Arbor (T.E.); the University of Pittsburgh, Pittsburgh (J.K.M.); Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom (S.J.W.); Merck, Kenilworth, NJ (S.T., E.K.P., R.F.P.); and the Center for Cancer Research, National Cancer Institute, Bethesda, MD (W.M.L., R.S.).
Sanjay ThamakeFrom the University of Texas M.D. Anderson Cancer Center, Houston (E.J.); Aarhus University Hospital, Aarhus, Denmark (F.D.); Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston (O.I.); Vanderbilt University Medical Center, Nashville (W.K.R.); University of Pennsylvania, Philadelphia (V.K.N.); the University of Utah, Salt Lake City (B.L.M.); Hôpital Européen Georges-Pompidou, University of Paris, Paris (S.O.); the University of Michigan, Ann Arbor (T.E.); the University of Pittsburgh, Pittsburgh (J.K.M.); Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom (S.J.W.); Merck, Kenilworth, NJ (S.T., E.K.P., R.F.P.); and the Center for Cancer Research, National Cancer Institute, Bethesda, MD (W.M.L., R.S.).
Eric K ParkFrom the University of Texas M.D. Anderson Cancer Center, Houston (E.J.); Aarhus University Hospital, Aarhus, Denmark (F.D.); Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston (O.I.); Vanderbilt University Medical Center, Nashville (W.K.R.); University of Pennsylvania, Philadelphia (V.K.N.); the University of Utah, Salt Lake City (B.L.M.); Hôpital Européen Georges-Pompidou, University of Paris, Paris (S.O.); the University of Michigan, Ann Arbor (T.E.); the University of Pittsburgh, Pittsburgh (J.K.M.); Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom (S.J.W.); Merck, Kenilworth, NJ (S.T., E.K.P., R.F.P.); and the Center for Cancer Research, National Cancer Institute, Bethesda, MD (W.M.L., R.S.).
Rodolfo F PeriniFrom the University of Texas M.D. Anderson Cancer Center, Houston (E.J.); Aarhus University Hospital, Aarhus, Denmark (F.D.); Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston (O.I.); Vanderbilt University Medical Center, Nashville (W.K.R.); University of Pennsylvania, Philadelphia (V.K.N.); the University of Utah, Salt Lake City (B.L.M.); Hôpital Européen Georges-Pompidou, University of Paris, Paris (S.O.); the University of Michigan, Ann Arbor (T.E.); the University of Pittsburgh, Pittsburgh (J.K.M.); Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom (S.J.W.); Merck, Kenilworth, NJ (S.T., E.K.P., R.F.P.); and the Center for Cancer Research, National Cancer Institute, Bethesda, MD (W.M.L., R.S.).
W Marston LinehanFrom the University of Texas M.D. Anderson Cancer Center, Houston (E.J.); Aarhus University Hospital, Aarhus, Denmark (F.D.); Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston (O.I.); Vanderbilt University Medical Center, Nashville (W.K.R.); University of Pennsylvania, Philadelphia (V.K.N.); the University of Utah, Salt Lake City (B.L.M.); Hôpital Européen Georges-Pompidou, University of Paris, Paris (S.O.); the University of Michigan, Ann Arbor (T.E.); the University of Pittsburgh, Pittsburgh (J.K.M.); Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom (S.J.W.); Merck, Kenilworth, NJ (S.T., E.K.P., R.F.P.); and the Center for Cancer Research, National Cancer Institute, Bethesda, MD (W.M.L., R.S.).
Ramaprasad SrinivasanFrom the University of Texas M.D. Anderson Cancer Center, Houston (E.J.); Aarhus University Hospital, Aarhus, Denmark (F.D.); Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston (O.I.); Vanderbilt University Medical Center, Nashville (W.K.R.); University of Pennsylvania, Philadelphia (V.K.N.); the University of Utah, Salt Lake City (B.L.M.); Hôpital Européen Georges-Pompidou, University of Paris, Paris (S.O.); the University of Michigan, Ann Arbor (T.E.); the University of Pittsburgh, Pittsburgh (J.K.M.); Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom (S.J.W.); Merck, Kenilworth, NJ (S.T., E.K.P., R.F.P.); and the Center for Cancer Research, National Cancer Institute, Bethesda, MD (W.M.L., R.S.).
MK-6482-004 Investigators
Aarhus University Hospital · DK

Funding

Novel Approaches to Targeting Cancers Associated with VHL MutationsZIABC011920 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI SRINIVASAN, RAMAPRASAD · 2019 to 2025
$4.1M
Developing a Translation Pipeline for VHL Mutant MalignanciesU01CA236489 · NCI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI David McDermott · 2019 to 2026
$3.8M
Intramural NIH HHS ZIA BC011920Medical Research Council MR/T024097/1NCI NIH HHS U01 CA236489
6 · The paper itself

Abstract

backgroundPatients with von Hippel-Lindau (VHL) disease have a high incidence of renal cell carcinoma owing to

methodsIn this phase 2, open-label, single-group trial, we investigated the efficacy and safety of the HIF-2α inhibitor belzutifan (MK-6482, previously called PT2977), administered orally at a dose of 120 mg daily, in patients with renal cell carcinoma associated with VHL disease. The primary end point was objective response (complete or partial response) as measured according to the Response Evaluation Criteria in Solid Tumors, version 1.1, by an independent central radiology review committee. We also assessed responses to belzutifan in patients with non-renal cell carcinoma neoplasms and the safety of belzutifan.

resultsAfter a median follow-up of 21.8 months (range, 20.2 to 30.1), the percentage of patients with renal cell carcinoma who had an objective response was 49% (95% confidence interval, 36 to 62). Responses were also observed in patients with pancreatic lesions (47 of 61 patients [77%]) and central nervous system hemangioblastomas (15 of 50 patients [30%]). Among the 16 eyes that could be evaluated in 12 patients with retinal hemangioblastomas at baseline, all (100%) were graded as showing improvement. The most common adverse events were anemia (in 90% of the patients) and fatigue (in 66%). Seven patients discontinued treatment: four patients voluntarily discontinued, one discontinued owing to a treatment-related adverse event (grade 1 dizziness), one discontinued because of disease progression as assessed by the investigator, and one patient died (of acute toxic effects of fentanyl).

conclusionsBelzutifan was associated with predominantly grade 1 and 2 adverse events and showed activity in patients with renal cell carcinomas and non-renal cell carcinoma neoplasms associated with VHL disease. (Funded by Merck Sharp and Dohme and others; MK-6482-004 ClinicalTrials.gov number, NCT03401788.).

Indexed as

AdultAgedAge of OnsetAnemiaAntineoplastic AgentsBasic Helix-Loop-Helix ProteinsCarcinoma, Renal CellDisease ProgressionFatigueFemaleFollow-Up StudiesHemangioblastomaHumansIndenesKidney NeoplasmsMaleAntineoplastic AgentsBasic Helix-Loop-Helix ProteinsbelzutifanIndenes

Identifiers

PMID34818478
PMCPMC9275515
OpenAlexW3215189579

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

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.