Michael J. Wagner, MD, assistant professor, University of Washington School of Medicine and Fred Hutchinson Cancer Research Center, explains how immunotherapy may be a promising treatment approach for patients with angiosarcoma.

There is a significant unmet medical need for new treatments in angiosarcoma, according to Wagner. There is no established standard of care for the disease, and efficacy of existing options is not as strong as desired, Wagner says.

Findings from small studies and case reports suggest that immunotherapy could address that unmet need, Wagner adds. For example, Wagner led the phase 2 DART trial (NCT02834013) evaluating ipilimumab (Yervoy) in combination with nivolumab (Opdivo) for patients with metastatic or unresectable angiosarcoma. 

One-quarter of patients in the trial responded to treatment, according to Wagner, who expresses excitement for what these findings could mean for the field going forward.

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Michael J. Wagner, MD, explains how immunotherapy may be a promising treatment approach for patients with angiosarcoma.

Dr Wagner or the Potential Value of Immunotherapy in Angiosarcoma

Michael J. Wagner, MD, assistant professor, University of Washington School of Medicine and Fred Hutchinson Cancer Research Center, discusses molecular pathways that are becoming relevant in angiosarcoma.

Recent breakthroughs in genetic sequencing have led to the identification of  molecular pathways that drive angiosarcoma, according to Wagner.

Investigators are exploring treatments targeting the MAPK pathway, as well as PIK3A, and mTOR, Wagner adds. Developing new agents can be challenging in angiosarcoma, but this knowledge may allow physicians to explore off-label regimens, Wagner concludes.

Michael J. Wagner, MD, discusses molecular pathways that are becoming relevant in angiosarcoma.

Dr Wagner on Molecular Pathways in Angiosarcoma

Michael J. Wagner, MD, assistant professor, University of Washington School of Medicine and Fred Hutchinson Cancer Research Center, discusses known risk factors for developing angiosarcoma.

Radiation exposure is a known cause of angiosarcoma, particuarly patients who have had breast-conserving therapy for breast cancer, according to Wagner. However, only a small fraction of those who are exposed to radiation in this way will eventually develop angiosarcoma, Wagner adds.

It has recently been discovered that exposure to ultraviolet light is associated with angiosarcoma, particularly when the disease presents on the face or scalp, Wagner says. Investigators have already started incorporating that information into their clinical trials, Wagner concludes. 

Michael J. Wagner, MD, discusses known risk factors for developing angiosarcoma.

Dr. Wagner on Risk Factors for Angiosarcoma

Michael J. Wagner, MD, assistant professor, University of Washington School of Medicine and Fred Hutchinson Cancer Research Center, discusses the standard of care for patients with angiosarcoma.

There is no established standard of care for angiosarcoma, according to Wagner. Part of the problem is that it is difficult to conduct large clinical trials with such a small patient population, Wagner says.

If the patient is eligible for surgery, angiosarcoma should be removed, Wagner adds. Chemoradiation is often administered, especially for patients with localized disease. Chemotherapy or targeted agents may be an option for those with metastatic angiosarcoma, Wagner concludes.

Michael J. Wagner, MD, discusses the standard of care for patients with angiosarcoma.

Dr. Wagner on the Standard of Care in Angiosarcoma

Michael J. Wagner, MD, assistant professor, University of Washington School of Medicine and Fred Hutchinson Cancer Research Center, discusses the challenge of diagnosing angiosarcoma.

Even as a specialist working in a referral center, Wagner only sees 15 to 20 patients with angiosarcoma in a given year. Diagnosing angiosarcoma is challenging because it can appear in almost every system in the body and the disease often looks like many other conditions.

Wagner says angiosarcoma can present as a bruise that does not go away or a purple lesion on the skin or scalp. Some patients experience pain at the site of the disease or, if angiosarcoma arises in the lungs, they may experience shortness of breath or cough.

Michael J. Wagner, MD, discusses the challenge of diagnosing angiosarcoma.

Dr. Wagner on Diagnosing Angiosarcoma

Michael J. Wagner, MD, assistant professor, University of Washington School of Medicine and Fred Hutchinson Cancer Research Center, discusses the importance of cooperative research groups in angiocarcinoma.

Angiosarcoma is a rare subset of an already rare disease, soft tissue sarcomas. Due to the lack of patients, it can be difficult for single institutions to recruit enough participants to conduct clinical trials.

Clinical trials requires collaboration, according to Wagner, who calls cooperative groups like EGOC, the Alliance, and SWOG "critical" for conducting research. Findings from the Angiosarcoma Project discovered the connection between exposure to ultraviolet light and angiosarcoma.

Michael J. Wagner, MD, discusses the importance of cooperative research groups in angiocarcinoma.

Dr. Wagner on the Value of Cooperative Research Groups in Angiosarcoma

Michael Wagner, MD, an assistant professor in the Clinical Research Division at Fred Hutchinson Cancer Research Center, discusses the rationale for using immunotherapy in the treatment of patients with 

A subset of patients with angiosarcomas have a higher tumor mutational burden, according to Wagner. These patients have mutations similar to those observed in melanomas, in which ultraviolet light damage has led to changes in the DNA of the disease that result in responsiveness to immunotherapy agents, Wagner says. This pattern was observed in certain subsets of patients with angiosarcoma, especially those with tumors of the skin that originated on the scalp or face, as well as those who have radiation-associated angiosarcomas, albeit to a lesser extent, Wagner explains.

Due to data indicating that this patient population may respond to immunotherapy, patients with angiosarcomas have been treated with different immunotherapeutic agents, Wagner notes. The biggest study to read out looked at 7 patients who were treated with immunotherapy and several of them responded to treatment, Wagner concludes.

Michael Wagner, MD, discusses the rationale for using immunotherapy in the treatment of patients with angiosarcoma.


Dr. Wagner on the Rationale for Immunotherapy in Angiosarcoma

Michael Wagner, MD, an assistant professor in the Clinical Research Division of Fred Hutchinson Cancer Research Center, discusses the safety profile of nivolumab (Opdivo) plus ipilimumab (Yervoy) in patients with angiosarcoma.

In the phase 2 DART trial (NCT02834013), no surprising safety signals were observed. The toxicity profile was in line with what had been expected from a nivolumab and ipilimumab combination, Wagner says. Most of the toxicities reported were autoimmune related; however, due to the small sample size of patients, it was difficult to generalize safety takeaways from the study, Wagner explains.

Overall, the study results did not indicate that patients with angiosarcoma are at higher risk for any particular toxicity, Wagner adds. A larger cohort would be needed to confirm this, Wagner concludes.

Michael Wagner, MD, discusses the safety profile of nivolumab plus ipilimumab in patients with angiosarcoma.


Dr. Wagner on the Safety Profile of Nivolumab/Ipilimumab in Angiosarcoma

Michael Wagner, MD, an assistant professor in the Clinical Research Division of Fred Hutchinson Cancer Research Center, discusses responses achieved in the phase 2 DART trial with nivolumab (Opdivo) plus ipilimumab (Yervoy) in patients with 

Of the 4 patients who responded to the combination therapy, 2 have continued on treatment with durable responses of around 1 year, according to Wagner. Notably, several other patients experienced prolonged disease stability with this approach and continue on therapy despite that their tumors did not technically respond to treatment, notes Wagner.

This is not typically seen in patients with metastatic angiosarcomas, Wagner says. Most patients who had received treatment with the doublet therapy were pretreated with chemotherapy or other therapies, Wagner concludes.

Michael Wagner, MD, discusses responses achieved with nivolumab plus ipilimumab in patients with angiosarcoma. 

Dr. Wagner on Responses Achieved With Nivolumab/Ipilimumab in Angiosarcoma

Michael Wagner, MD, an assistant professor in the Clinical Research Division of Fred Hutchinson Cancer Research Center, discusses future research efforts in sarcoma subtypes.

The field of sarcoma is moving toward being more compartmentalized in terms of treatment, according to Wagner. As more is learned about sarcoma through large-scale collaborative efforts, a key focus is to determine what drives subtypes like angiosarcoma, leiomyosarcoma, desmoid fibromatosis, and epithelioid sarcoma, says Wagner. 

Each subtype is very different, but they have all historically been treated in the same way for pragmatic reasons, explains Wagner. These subtypes are rare and a certain number of patients need to be enrolled on clinical trials to learn more about them, which presents a challenge, Wagner adds. However, scientific advances have sparked more opportunities for collaborative research efforts in this area, Wagner concludes.

Michael Wagner, MD, discusses future research efforts in sarcoma subtypes.

Dr. Wagner on Future Research Efforts in Sarcoma Subtypes

Michael Wagner, MD, an assistant professor in the Clinical Research Division of Fred Hutchinson Cancer Research Center, discusses the potential use of immunotherapy in patients with 

Several research efforts have shed light on the molecular changes that occur in different sarcoma subtypes. Now, some early data examining immunotherapy in patients with angiosarcoma suggest potential efficacy with this approach, according to Wagner. One particular effort known as the Angiosarcoma Project, which was patient-driven and conducted at the Broad Institute, collected hundreds of samples from patients with the disease; these samples were then molecularly sequenced to identify molecular changes.

Investigators were able to identify a subset of patients with angiosarcoma who have a high tumor mutational burden similar to that of skin cancers such as melanoma, where ultraviolet light leads to changes in the cancer, says Wagner. This could play a part in why these cancers respond to immunotherapy, Wagner concludes.

Michael Wagner, MD, discusses the potential use of immunotherapy in patients with angiosarcoma.

Michael Wagner, MD

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