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 angiosarcoma.

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.

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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 angiosarcoma. 

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 angiosarcoma.

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

Articles

Dr. Wagner on the Rationale for Immunotherapy in Angiosarcoma

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

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

Dr. Wagner on Future Research Efforts in Sarcoma Subtypes

Dr. Wagner on the Potential for Immunotherapy in Angiosarcoma