Patient-Partnered Genomics Study Identifies Immunotherapy as a Potential Treatment for Angiosarcomas
Angiosarcoma of the head, face, neck, or scalp is a rare cancer associated with high rates of local recurrence, distant metastasis, and poor prognosis. Because angiosarcoma is so rare, it is difficult to conduct large-scale research in the cancer. To address this issue, the Broad Institute of MIT and Harvard has launched the Angiosarcoma Project, a patient-powered genomics study that seeks to empower patients to accelerate research by remotely sharing their saliva, blood, and tissue samples and clinical information. From the patient data analyzed, the researchers were able to identify immune checkpoint inhibitors as a potential treatment option for patients with angiosarcomas of the head, face, neck, or scalp.
The researchers’ findings suggest a common genomic basis for head, face, neck, or scalp angiosarcoma and could provide a rationale for clinical interventions using checkpoint inhibitors for this rare cancer. The study by Painter, et al was presented at the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival (Abstract B085).
Study Methodology
The researchers developed a website, ASCproject.org, where patients from the United States and Canada can remotely share their medical records, saliva, blood, and archival tissue. The researchers then performed whole-exome sequencing of about 20,000 genes on tumor and matched germline DNA. The genomic data are combined with the clinical data, including diagnosis, treatments, and responses, to generate a clinically annotated genomic database that is shared publicly. The goal is to identify the genomic drivers of the disease and mechanisms of response and resistance to treatments.
Since the study launched in March of 2017, 321 patients with angiosarcoma have registered on the site. Primary locations of the cancer were primary breast (24%); breast with prior radiation (20%); head/face/neck/scalp (21%); bone/limb (9%); abdominal (3%); heart (3%); lung (1%); liver (1%); lymph node (0.5%); multiple locations (11%); and other locations (5%). A total of 142 patients (48%) reported being disease-free at the time of enrollment.
Study Results
The researchers identified several genes in the samples known to be altered in angiosarcoma, including KDR and TP53. All three patients with angiosarcoma of the head, face, neck, or scalp from the initial cohort of 12 patients in the first data release had tumors with a high tumor mutational burden (more than 150 mutations/kb) and dominant ultraviolet light signature, similar to melanoma. Recent studies have shown that patients with tumors bearing a high mutational burden are more likely to respond to immune checkpoint inhibitors targeting programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1).
Through the patient portal, the researchers identified an additional 56 patients with head/face/neck/scalp angiosarcoma. Two patients had received the anti–PD-1 antibody pembrolizumab (Keytruda) off-label to treat metastatic disease. Both of these patients had complete and durable responses to the treatment and remained without evidence of disease at the time of publication of this study.
“These findings suggest a common genomic basis for [head/face/neck/scalp angiosarcoma] and could provide rationale for clinical interventions using checkpoint inhibitors for these [angiosarcomas]. Analyses of additional samples are underway to further characterize mutational signatures in [head/face/neck/scalp angiosarcoma] and implications for patient care. This study serves as proof of principle that patient-partnered genomics efforts can democratize cancer research for exceedingly rare cancers,” concluded the study researchers.
The study was funded by the Broad Institute.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
