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New Molecular Insights, and the Role of Systemic Therapies and Collaboration for Treatment of Epithelioid Hemangioendothelioma (EHE)

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Opinion statement

Epithelioid hemangioendothelioma (EHE) is an ultra-rare, translocated vascular sarcoma. EHE can have different clinical presentations from indolent to rapidly evolving cases, behaving as a high-grade sarcoma. Serosal effusion and systemic symptoms such as fever and severe pain are known as adverse prognostic factors; however, outcome prediction at disease onset remains a major challenge. In spite of its rarity, an international collaborative effort is in place with the support of patient advocates to increase the knowledge of EHE biology, develop new treatment options, and improve patient access to new active medications. Currently, systemic therapies are indicated only for patients suffering from progressive and/or symptomatic disease and in patients with a high risk of organ dysfunction. Standard systemic agents available so far for treatment of sarcomas, and in particular anthracycline-based chemotherapy, have marginal activity in EHE. On this background, EHE patients should be always considered for clinical study when available. The MEK inhibitor trametinib has been recently investigated prospectively in advanced EHE showing some activity, but the publication of the full dataset is still awaited to better interpret the results. Besides, there are data on response to antiangiogenics such as sorafenib and bevacizumab and, from retrospective studies, interferon, thalidomide, and sirolimus. Unfortunately, none of these agents is formally approved for EHE patients and access to treatments varies greatly between countries causing a huge disparity in patient care from one country to another.

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Authors and Affiliations

  1. Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale Dei Tumori, Via G. Venezian 1, 20133, Milan, Italy

    Silvia Stacchiotti MD

  2. Department of Medicine, Memorial Sloan Kettering Cancer Center, New York City, USA

    William Tap MD

  3. Chair of Trustees of the EHE Rare Cancer Charity UK, Charity Number 1162472, Kingston-Upon-Thames, UK

    Hugh Leonard

  4. Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milan, Italy

    Nadia Zaffaroni PhD

  5. Department of Medical Oncology, Santo Stefano Hospital, Prato, Italy

    Giacomo G Baldi MD

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Correspondence to Silvia Stacchiotti MD.

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Conflict of Interest

None of the authors has any interest to report directly related to this manuscript.

Outside the scope of this manuscript:

Silvia Stacchiotti reports honoraria from Aadi, Boehringer, Glaxo Smith Kline, Pharmamar, Gentili; participation on a Data Safety Monitoring Board or Advisory Board for Astex Pharmaceuticals, Bayer, Bavarian Nordic, Boehringer, Daiichi Sankyo, Glaxo Smith Kline, Ikena, Maxivax, Novartis, PharmaMar, Rain Therapeutic, Servier, SpringWorks; support for attending meetings and/or travel Pharmamar; unpaid leadership in Member of the Scientific Advisory Board of the Chordoma Foundation, Member of the Scientific Advisory Board of the Desmoid Foundation, Member of the Scientific Advisory Board of the Epithelioid Hemangioendothelioma Group, Member of the Scientific Advisory Board of the Leiomyosarcoma Foundation.

William Tap reports personal fees from Eli Lilly, personal fees from EMD Serono, personal fees from Mundipharma, personal fees from C4 Therapeutics, personal fees from Daiichi Sankyo, personal fees from Deciphera, personal fees from Adcendo, personal fees from Ayala Pharmaceuticals, personal fees from Kowa, personal fees from Servier, personal fees from Bayer Pharmaceuticals, personal fees from Epizyme, personal fees from Cogent, personal fees from Medpacto, personal fees from Foghorn Therapeutics, personal fees from Amgen, personal fees from AmMax Bio, personal fees from Boehringer Ingelheim, personal fees from BioAtla, personal fees from Inhibrx, outside the submitted work; In addition, Dr. Tap has a patent Companion Diagnostic for CDK4 inhibitors—14/854,329 pending to MSKCC/SKI, and a patent Enigma and CDH18 as companion Diagnostics for CDK4 inhibition—SKI2016-021–03 pending to MSKCC/SKI and Scientific Advisory Board—Certis Oncology Solutions, Stock OwnershipÜo-Founder—Atropos Therapeutics, Stock Ownership-Scientific Advisory Board Innova Therapeutics.

Hugh Leonard: No conflict of interest to declare.

Nadia Zaffaroni: Research funding to my institution for studies in which I am involved: Ikena.

Giacomo G Baldi reports consulting fees from Eli Lilly, Pharmamar, AboutEvents, Boehringer Ingelheim; honoraria from Pharmamar, Eli Lilly, Glaxo Smith Kline, Merck Sharp & Dome, Eisai; support for attending meetings and/or travels from Novartis, Pharmamar, Eli Lilly; participation on advisory board from Pharmamar, Eli Lilly, Glaxo Smith Kline, Merck Sharp & Dome, Eisai, Boehringer Ingelheim, outside the submitted work.

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All reported studies/experiments with human or animal subjects performed by the authors have been previously published and complied with all applicable ethical standards (including the Helsinki declaration and its amendments, institutional/national research committee standards, and international/national/institutional guidelines).

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Stacchiotti, S., Tap, W., Leonard, H. et al. New Molecular Insights, and the Role of Systemic Therapies and Collaboration for Treatment of Epithelioid Hemangioendothelioma (EHE). Curr. Treat. Options in Oncol. 24, 667–679 (2023). https://doi.org/10.1007/s11864-023-01076-1

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