The DOI matches its Crossref record; 22 of the 22 references it cites were found in a registry or an index.
Belzutifan for Renal Cell Carcinoma in von Hippel–Lindau Disease
Open accessAbstract
BACKGROUND: gene inactivation and constitutive activation of the transcription factor hypoxia-inducible factor 2α (HIF-2α). METHODS: In 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. RESULTS: After 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). CONCLUSIONS: Belzutifan 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.).
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“PT2977/belzutifan was recently approved by the FDA for the treatment of RCC in patients with von Hippel-Lindau syndrome (47, 48).”
From HIF inhibitor 32-134D eradicates murine hepatocellular carcinoma in combination with anti-PD1 therapy (2022) · cites this paper as [48]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The most frequent on-target toxicity with HIF-2 inhibitors (PT2385; belzutifan) is anemia from suppression of renal/hepatic erythropoietin.”
From HIF inhibition: Current strategies and clinical challenges (2026) · cites this paper as [421]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Anemia occurred commonly in early trials and, during prolonged belzutifan therapy, occasionally required transfusion or erythropoiesis-stimulating agents, hence the need for routine hematological monitoring [37,412,421].”
From HIF inhibition: Current strategies and clinical challenges (2026) · cites this paper as [421]
In the citing paper
“VHL gene mutations lead to the stability of HIF subunits and the constitutive activation of HIF‐mediated transcriptional pathways in patients with VHL, causing the progression of renal cell carcinoma.”
From Hypoxia signaling in cancer: Implications for therapeutic interventions (2023) · cites this paper as [24]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
von Hippel–Lindau disease: A clinical and scientific review
Maher, E. R., Neumann, H. P. H., & Richard, S. (2011) · European Journal of Human Genetics · doi:10.1038/ejhg.2010.175 · Cited by 744
Targeting renal cell carcinoma with a HIF-2 antagonist
Chen, W., Hill, H., Christie, A., Kim, M. S., Holloman, E., Pavia-Jimenez, A., Homayoun, F., Ma, Y., Patel, N., Yell, P., et al. (2016) · Nature · doi:10.1038/nature19796 · Cited by 709
Hypoxia-inducible factor-2 (HIF-2) regulates hepatic erythropoietin in vivo
Rankin, E. B., Biju, M. P., Liu, Q., Unger, T. L., Rha, J., Johnson, R. S., Simon, M. C., Keith, B., & Haase, V. H. (2007) · Journal of Clinical Investigation · doi:10.1172/jci30117 · Cited by 596
Targeting the HIF2–VEGF axis in renal cell carcinoma
Choueiri, T. K., & Kaelin, W. G. (2020) · Nature Medicine · doi:10.1038/s41591-020-1093-z · Cited by 477 · cited 1×
“Upper respiratory tract infection 11 (18) 4 (7) 7 (11) 0”
On-target efficacy of a HIF-2α antagonist in preclinical kidney cancer models
Cho, H., Du, X., Rizzi, J. P., Liberzon, E., Chakraborty, A. A., Gao, W., Carvo, I., Signoretti, S., Bruick, R. K., Josey, J. A., et al. (2016) · Nature · doi:10.1038/nature19795 · Cited by 451 · cited 1×
“Alanine aminotransferase level increase 10 (16) 10 (16) 0 0”
BackgroundCourtney, K. D., Infante, J. R., Lam, E. T., Figlin, R. A., Rini, B. I., Brugarolas, J., Zojwalla, N. J., Lowe, A. M., Wang, K., Wallace, E. M., et al. (2018) · Journal of Clinical Oncology · doi:10.1200/jco.2017.74.2627 · Cited by 393
Choueiri, T. K., Bauer, T. M., Papadopoulos, K. P., Plimack, E. R., Merchan, J. R., McDermott, D. F., Michaelson, M. D., Appleman, L. J., Thamake, S., Perini, R. F., et al. (2021) · Nature Medicine · doi:10.1038/s41591-021-01324-7 · Cited by 305 · cited 1×
“Upper respiratory tract infection 11 (18) 4 (7) 7 (11) 0”
Self-citationPharmacologic Targeting of Hypoxia-Inducible Factors
Semenza, G. L. (2019) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010818-021637 · Cited by 288
HIF-2α regulates murine hematopoietic development in an erythropoietin-dependent manner
Scortegagna, M., Ding, K., Zhang, Q., Oktay, Y., Bennett, M. J., Bennett, M., Shelton, J. M., Richardson, J. A., Moe, O. W., & Garcia, J. A. (2004) · Blood · doi:10.1182/blood-2004-05-1695 · Cited by 237
Courtney, K. D., Ma, Y., Diaz de Leon, A., Christie, A., Xie, Z., Woolford, L., Singla, N., Joyce, A., Hill, H., Madhuranthakam, A. J., et al. (2020) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-19-1459 · Cited by 188
Flagged first, then by citations
Cited by
Sorted by citations
Items 701–717 of 717
Hussain, M. A., Daniel, S., Varghese, S. S., Chapla, A., Prisca Santhanam, A., Asha, H. S., Jebasingh, F., & Thomas, N. (2026) · AACE Endocrinology and Diabetes · doi:10.1016/j.aed.2026.09.013
Wei, L., 胡玉清, Lyu, Y., Qian, H., Qin, H., Wu, Y., & Zhang, X. (2026) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6c01656
Sinan, H., Sleiman, E. A., Blackford, A. L., Shinozuka, T., Melki, D., Saab, J., Romanos, M., Ning, K., Almardini, M., Castellino, A., et al. (2026) · Pancreatology · doi:10.1016/j.pan.2026.10.013
Belzutifan in der Behandlung des Nierenzellkarzinoms
Büttner, T. (2026) · Die Urologie · doi:10.1007/s00120-026-02939-9
Yin, Y., Wang, J., Li, D., & Qiu, D. (2026) · Frontiers in Oncology · doi:10.3389/fonc.2026.1952158
Niches in cancer: from primary tumors to metastatic disease
Chao, Z., Wang, X., Wang, Z., Wu, K., & Li, L. (2026) · Journal of Hematology & Oncology · doi:10.1186/s13045-026-01858-8
Bayrak, B. Y., Özsağır, E., Yıldırım, N. A., Teke, K., Cheng, M., Caliò, A., Martignoni, G., Akgül, M., & Liang Cheng, C. (2026) · Cancers · doi:10.3390/cancers18203341
“In ccRCC, VHL pathway inactivation provides the biological basis for established VEGF-targeted therapies and HIF2 α inhibition [94–96].”
Yaşar, Ş., Yağın, F. H., Alzakari, S. A., Alkhalifa, A. K., Al-Hashem, F. H., & Tabnjh, A. K. (2026) · Life · doi:10.3390/life16101752
Takeuchi, K., Okamoto, T., Sekine, Y., Shinohara, M., Tamaki, G., Abe, N., Kobayashi, S., Fujita, N., Sato, S., Habuchi, T., et al. (2026) · Clinical Genitourinary Cancer · doi:10.1016/j.clgc.2026.102699
HIF-2α in Lung Biology and Disease: From Adaptation and Repair to Therapeutic Modulation
Man, H. S. J., Saha, A. D., Wu, L., & de Perrot, M. E. (2026) · Biology · doi:10.3390/biology15211907
Efficacy of Oral Belzutifan for Retinal Capillary Hemangioblastomas in von Hippel-Lindau Disease
Ji, M. H., Thavikulwat, A. T., Agrón, E., Hébert, M., Indurkar, A., Ward, C., Emamverdi, M., Keenan, T. D. L., & Chew, E. Y. (2026) · Ophthalmology Retina · doi:10.1016/j.oret.2026.10.008
Heng, D. Y. C., Schmidinger, M., McDermott, R., Park, S. H., Burotto, M., Ciccarese, C., Verzoni, E., Suárez, C., Eto, M., Cutuli, H. J., et al. (2026) · Annals of Oncology · doi:10.1016/j.annonc.2026.10.109
Self-citationBureau, B. L., Shahbandi, A., Shabani, S., & Connelly, J. (2026) · Frontiers in Oncology · doi:10.3389/fonc.2026.1935078
Recent Therapeutic Improvements in Pediatric Oncology: One Fellow Generation (2020–2025)
Quintero-García, D., Seguí, A., Palau, A. G., Pablos, A., Nadal, M., Vega, A. I., Bueno, I., Cañada, M. D., Suarez, R. P., Iriondo, M., et al. (2026) · Cancers · doi:10.3390/cancers18213447
Advances in the management of renal cell carcinoma
Lewis, A. R., Lyon, T. D., Gupta, S., Zakharia, Y., Leibovich, B. C., & Costello, B. A. (2026) · BMJ · doi:10.1136/bmj-2026-100785
Lee, C., Byeon, Y., Kim, K., Lee, W., Hwang, K., Dho, Y., Sung, K. S., Roh, T. H., Chong, K., Park, K., et al. (2026) · Brain Tumor Research and Treatment · doi:10.14791/btrt.2026.0009
BindingDB Entry 50019394: Discovery of Cycloalkyl[
BindingDB (2024) · UC San Diego · doi:10.7270/q2k3601n
Metadata
- Authors
- Jonasch, E., Donskov, F., Iliopoulos, O., Rathmell, W. K., Narayan, V. K., Maughan, B. L., Oudard, S., Else, T., Maranchie, J. K., Welsh, S. J., Thamake, S., Park, E. K., Perini, R. F., Linehan, W. M., & Srinivasan, R.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- From 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.).
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2021-11-25
- Volume
- 385
- Issue
- 22
- Pages
- 2036-2046
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- PMC
- PMC9275515
- OpenAlex
- W3215189579
- Cited by
- 714
- References
- 22
- Citations by year
- 2026: 140 · 2025: 167 · 2024: 135 · 2023: 140 · 2022: 128 · 2021: 4
- FWCI
- 66.14
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA
- Topics
- Health Sciences › Medicine › Oncology › Renal cell carcinoma treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Health Sciences › Medicine › Oncology › Ear and Head Tumors
- Keywords
- belzutifan, HIF-2α inhibition, von Hippel-Lindau disease, renal cell carcinoma, hemangioblastoma, retinal hemangioblastoma, pancreatic lesions, anemia, drug safety, objective response
- MeSH terms
- Adult, Aged, Anemia, Antineoplastic Agents, Carcinoma, Renal Cell, Fatigue, Female, Follow-Up Studies, von Hippel-Lindau Disease, Humans, Indenes, Kidney Neoplasms, Male, Middle Aged, Neoplasms, Multiple Primary, Pancreatic Neoplasms, Age of Onset, Hemangioblastoma, Neuroendocrine Tumors, Disease Progression, Basic Helix-Loop-Helix Proteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
