Current and Future Directions for Angiosarcoma Therapy
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Angiosarcomas are rare vascular neoplasms that are among the most aggressive subtypes of soft tissue sarcomas. Surgical resection is often challenging even in localized disease, as the infiltrative nature of these cancers leads to frequent local and metastatic recurrences. Cytotoxic chemotherapy, including anthracycline-based regimens and taxanes can produce significant responses in a subset of patients but durability is limited with most patients ultimately succumbing to metastatic disease. Targeted therapy with tyrosine kinase inhibitors is usually well-tolerated but prone to development of resistance. Few head-to-head trials have addressed the optimal sequence of therapies, or demonstrated conclusive benefits of one therapy over another based on clinical and etiologic factors. Novel therapies in clinical trials, including antibodies to endoglin and checkpoint inhibitors have demonstrated exciting early activity in patients with angiosarcoma. Improved understanding of the genetic heterogeneity within various angiosarcoma subtypes may identify predictive biomarkers to match patients to effective existing and future therapies. Overall, angiosarcoma patients with optimal performance status are best served in clinical trials that incorporate novel combinations of cytotoxic chemotherapy, targeted therapies, and immunotherapies.
KeywordsAngiosarcoma Targeted therapy Chemotherapy Clinical trials Immunotherapy
Compliance with Ethical Standards
Conflict of Interest
Vaia Florou declares that she has no conflict of interest.
Breelyn A. Wilky has received research support through a grant from Merck, and has received compensation from Novartis, Janssen Oncology, and Lilly for service as a consultant.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
References and Recommended Reading
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- 14.• Ravi V, Ramesh N, Patnana M, et al. Whole-exome and targeted sequencing of angiosarcomas: target identification and treatment implications. J Clin Oncol. 2014 p 32:5s (suppl; abstr 10512). First studies reporting results of whole exome sequencing of angiosarcomas.Google Scholar
- 26.•• Young RJ, Natukunda A, Litière S, Woll PJ, Wardelmann E, Van Der Graaf WTA. First-line anthracycline-based chemotherapy for angiosarcoma and other soft tissue sarcoma subtypes: pooled analysis of eleven European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group trials. Eur J Cancer. 2014;50:3178–86. Standard of care regimen for angiosarcoma.CrossRefPubMedGoogle Scholar
- 27.•• Tap WD, Jones RL, Van Tine BA, et al. Olaratumab and doxorubicin versus doxorubicin alone for treatment of soft-tissue sarcoma: an open-label phase 1b and randomised phase 2 trial. Lancet. 2016;388:488–97. New standard of care in the treatment of metastatic sarcomas.CrossRefPubMedPubMedCentralGoogle Scholar
- 37.Maki RG, Wathen JK, Patel SR, et al. Randomized phase II study of gemcitabine and docetaxel compared with gemcitabine alone in patients with metastatic soft tissue sarcomas: results of sarcoma alliance for research through collaboration study 002. J Clin Oncol. 2007;25:2755–63.CrossRefPubMedGoogle Scholar
- 38.Pautier P, Floquet A, Penel N, et al. Randomized multicenter and stratified phase II study of gemcitabine alone versus gemcitabine and docetaxel in patients with metastatic or relapsed leiomyosarcomas: a Federation Nationale des Centres de Lutte Contre le Cancer (FNCLCC) French Sarcoma Group. Oncologist. 2012;17:1213–20.CrossRefPubMedPubMedCentralGoogle Scholar
- 54.Daguzé J, Saint-Jean M, Dréno B. Large nose angiosarcoma treated effectively with oral cyclophosphamide combined with propranolol. J Eur Acad Dermatol Venereol. 2017;12:3218–21.Google Scholar
- 58.Sankhala KK, Attia S, Barve M, Wright J, Riedel R, Robinson S, et al. TRC105 (endoglin antibody) in combination with pazopanib in patients with advanced angiosarcoma. In: Connect. Tissue Oncol. Soc. p Poster 110. 2016.Google Scholar
- 59.• Tawbi HA, Burgess M, Bolejack V, et al. Pembrolizumab in advanced soft-tissue sarcoma and bone sarcoma (SARC028): a multicentre, two-cohort, single-arm, open-label, phase 2 trial. Lancet Oncol. 2017;2045:1–9. First trial on the efficacy of checkpoint inhibition in advanced soft tissue and bone sarcomas.Google Scholar
- 62.Somaiah N, Anthony C, Lin H, et al. A phase II multi-arm study to test the efficacy of immunotherapeutic agents in multiple sarcoma subtypes. In: Connect. Tissue Oncol. Soc. p Paper 010. 2017.Google Scholar
- 63.Angiosarcoma Project. https://ascproject.org/home.