Evidence map›Paper›PMID 34380663›Full record

Trial reportJournal for immunotherapy of cancer2021

Multicenter phase II trial (SWOG S1609, cohort 51) of ipilimumab and nivolumab in metastatic or unresectable angiosarcoma: a substudy of dual anti-CTLA-4 and anti-PD-1 blockade in rare tumors (DART).

Michael J Wagner, Megan Othus, Sandip P Patel, Chris Ryan, Ashish Sangal, Benjamin Powers, G Thomas Budd, Adrienne I Victor, Chung-Tsen Hsueh, Rashmi Chugh and 10 more

Registry-linked trialOpen access · goldAbstract readClinical Trial, Phase IIMulticenter Study
In one paragraph

Trial report in Journal for immunotherapy of cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02834013 (DART), which is not on this map. Cited by 101 papers.

0numbers the graph read from it
0cells of the map it votes in
101citing papers in PubMed
9.1field-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.

NCT02834013 phase2active not recruitingnot on this map

DART: Dual Anti-CTLA-4 and Anti-PD-1 Blockade in Rare Tumors

TypeinterventionalSponsorNational Cancer Institute (NCI)Ran2017 to 2027Enrolled798ConditionsAcinar Cell Carcinoma, Adenoid Cystic Carcinoma, Adrenal Cortical Carcinoma, Adrenal Gland PheochromocytomaArmsBiospecimen Collection, Computed Tomography, Echocardiography Test, Ipilimumab, Magnetic Resonance Imaging
3 · Its place in the literature

Who cites it

101 citing papers in PubMed, 151 citations in OpenAlex.

  1. Trial
  2. Cemiplimab in Locally Advanced or Metastatic Secondary Angiosarcomas (CEMangio): A Phase II Clinical Trial and Biomarker Analyses.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025
    Trial
  3. Trial
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  6. A Phase II Basket Trial of Dual Anti-CTLA-4 and Anti-PD-1 Blockade in Rare Tumors SWOG S1609: Vulvar Cancers.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025
    Trial
  7. SWOG/NCI Phase II Dual Anti-CTLA-4/PD-1 Blockade in Rare Tumors: Nonepithelial Ovarian Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024
    Trial
  8. Trial
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  11. Phase II Study of Eribulin plus Pembrolizumab in Metastatic Soft-tissue Sarcomas: Clinical Outcomes and Biological Correlates.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024
    Trial
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  13. Trial
  14. A Phase 1/2 Trial Combining Avelumab and Trabectedin for Advanced Liposarcoma and Leiomyosarcoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022
    Trial
  15. Trial
  16. Review
  17. Review
  18. Article
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  20. Article

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

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 at 15 institutions in 1 country.

Michael J WagnerClinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA wagnermj@uw.edu.ORCID 0000-0002-0753-9282
Megan OthusSWOG Statistical and Data Management Center/Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Sandip P PatelDepartment of Medicine, UCSD Moores Cancer Center, La Jolla, California, USA.
Chris RyanDepartment of Medicine, OHSU, Portland, Oregon, USA.
Ashish SangalWestern Regional Medical Center, Goodyear, Arizona, USA.
Benjamin PowersDepartment of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas, USA.
G Thomas BuddHematology and Medical Oncology, Cleveland Clinic, Cleveland, Ohio, USA.
Adrienne I VictorDepartment of Medicine, University of Rochester, Rochester, New York, USA.
Chung-Tsen HsuehLoma Linda University, Loma Linda, California, USA.
Rashmi ChughDepartment of Medicine, University of Michigan, Ann Arbor, Michigan, USA.
Suresh NairLehigh Valley Health Network, Allentown, Pennsylvania, USA.
Kirsten M LeuNebraska Methodist Health System, Omaha, Nebraska, USA.
Mark AgulnikMedical Oncology & Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, California, USA.
Elad SharonCancer Therapy Evaluation Program, National Cancer Institute, Bethesda, Maryland, USA.ORCID 0000-0002-0044-9719
Edward MayersonSWOG Statistical and Data Management Center/Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Melissa PletsSWOG Statistical and Data Management Center/Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Charles BlankeDepartment of Medicine, OHSU, Portland, Oregon, USA.
Howard StreicherCancer Therapy Evaluation Program, National Cancer Institute, Bethesda, Maryland, USA.
Young Kwang ChaeDepartment of Medicine, Northwestern University, Chicago, Illinois, USA.
Razelle KurzrockDepartment of Medicine, UCSD Moores Cancer Center, La Jolla, California, USA.
Fred Hutch Cancer Center · USMoores Cancer CenterNational Cancer Institute · USNorthwestern University · USCleveland Clinic · USGoodyear (United States) · USLehigh Valley Hospital-Pocono · USLoma Linda University · USNebraska Methodist College · USSWOG Cancer Research Network · USUniversity of Kansas Medical Center · USUniversity of Michigan · USUniversity of Portland · USUniversity of Rochester · USUniversity of Washington Medical Center · US

Funding

NRG Oncology Network Group Operations Center - GY9 BIQSFP Reports/BudgetsU10CA180868 · NCI · NRG ONCOLOGY FOUNDATION, INC. · PI NORMAN WOLMARK · 2014 to 2026
$206.8M
SWOG Network Group Operations Center of the NCTNU10CA180888 · NCI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI PRIMO N. LARA · 2014 to 2026
$152.1M
SWOG Statistics & Data Management Center complex - extension supplement for GY06U10CA180819 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Michael L. LeBlanc · 2014 to 2026
$115.2M
UM LAPs -UG1 GrantUG1CA233160 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ANNE F SCHOTT · 2019 to 2026
$5.4M
NCI NIH HHS U10 CA180819NCI NIH HHS U10 CA180868NCI NIH HHS U10 CA180888NCI NIH HHS UG1 CA233160
6 · The paper itself

Abstract

purposeAngiosarcoma is a rare aggressive endothelial cell cancer with high mortality. Isolated reports suggest immune checkpoint inhibition efficacy in angiosarcoma, but no prospective studies have been published. We report results for angiosarcoma treated with ipilimumab and nivolumab as a cohort of an ongoing rare cancer study.

methodsThis is a prospective, open-label, multicenter phase II clinical trial of ipilimumab (1 mg/kg intravenously every 6 weeks) plus nivolumab (240 mg intravenously every 2 weeks) for metastatic or unresectable angiosarcoma. Primary endpoint was objective response rate (ORR) per RECIST 1.1. Secondary endpoints include progression-free (PFS) and overall survival, and toxicity. A two-stage design was used.

resultsOverall, there were 16 evaluable patients. Median age was 68 years (range, 25-81); median number of prior lines of therapy, 2. Nine patients had cutaneous and seven non-cutaneous primary tumors. ORR was 25% (4/16). Sixty per cent of patients (3/5) with primary cutaneous scalp or face tumors attained a confirmed response. Six-month PFS was 38%. Altogether, 75% of patients experienced an adverse event (AE) (at least possibly related to drug) (25% grade 3-4 AE); 68.8%, an immune-related AE (irAE) (2 (12.5%), grade 3 or 4 irAEs (alanine aminotransferase/aspartate aminotransferase increase and diarrhea)). There were no grade 5 toxicities. One of seven patients in whom tumor mutation burden (TMB) was assessed showed a high TMB (24 mutations/mb); that patient achieved a partial response (PR). Two of three patients with PDL1 immunohistochemistry assessed had high PDL1 expression; one achieved a PR.

conclusionThe combination of ipilimumab and nivolumab demonstrated an ORR of 25% in angiosarcoma, with three of five patients with cutaneous tumors of the scalp or face responding. Ipilimumab and nivolumab warrant further investigation in angiosarcoma. TRIAL REGISTRATION NUMBER: NCT02834013.

Indexed as

AdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsCTLA-4 AntigenFemaleHemangiosarcomaHumansImmune Checkpoint InhibitorsIpilimumabMaleMiddle AgedNeoplasm MetastasisNivolumabProspective StudiesRare DiseasesCTLA-4 AntigenCTLA4 protein, humanImmune Checkpoint InhibitorsIpilimumabNivolumabClinical TrialsCombinationDrug TherapyImmunotherapyPhase II as TopicSarcoma

Identifiers

PMID34380663
PMCPMC8330584
OpenAlexW3099993684

What OpenQuestion holds

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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.