RT Journal Article
SR Electronic
T1 Angiosarcoma patients treated with immune checkpoint inhibitors: a case series of seven patients from a single institution
JF Journal for ImmunoTherapy of Cancer
JO J Immunother Cancer
FD BMJ Publishing Group Ltd
SP 213
DO 10.1186/s40425-019-0689-7
VO 7
IS 1
A1 Vaia Florou
A1 Andrew E. Rosenberg
A1 Eric Wieder
A1 Krishna V. Komanduri
A1 Despina Kolonias
A1 Mohamed Uduman
A1 John C. Castle
A1 Jennifer S. Buell
A1 Jonathan C. Trent
A1 Breelyn A. Wilky
YR 2019
UL http://jitc.bmj.com/content/7/1/213.abstract
AB Background Angiosarcoma is an uncommon endothelial malignancy and a highly aggressive soft tissue sarcoma. Due to its infiltrative nature, successful management of localized angiosarcoma is often challenging. Systemic chemotherapy is used in the metastatic setting and occasionally in patients with high-risk localized disease in neoadjuvant or adjuvant settings. However, responses tend to be short-lived and most patients succumb to metastatic disease. Novel therapies are needed for patients with angiosarcomas.Methods We performed a retrospective analysis of patients with locally advanced or metastatic angiosarcoma, who were treated with checkpoint inhibitors at our institution. We collected their clinical information and outcome measurements. In one patient with achieved complete response, we analyzed circulating and infiltrating T cells within peripheral blood and tumor tissue.Results We have treated seven angiosarcoma (AS) patients with checkpoint inhibitors either in the context of clinical trials or off label [Pembrolizumab + Axitinib (NCT02636725; n = 1), AGEN1884, a CTLA-4 inhibitor (NCT02694822; n = 2), Pembrolizumab (n = 4)]. Five patients had cutaneous angiosarcoma, one primary breast angiosarcoma and one radiation-associated breast angiosarcoma. At 12 weeks, 5/7 patients (71%) had partial response of their lesions either on imaging and/or clinical exam and two (29%) had progressive disease. 6/7 patients are alive to date and, thus far, 3/7 patients (43%) have progressed (median 3.4 months)- one achieved partial response after pembrolizumab was switched to ongoing Nivolumab/Ipilimumab, one died of progressive disease at 31 weeks (primary breast angiosarcoma) and one was placed on pazopanib. One patient had a complete response (CR) following extended treatment with monotherapy AGEN1884. No patient experienced any ≥ grade 2 toxicities.Conclusions This case series underscores the value of targeted immunotherapy in treating angiosarcoma. It also identifies genetic heterogeneity of cutaneous angiosarcomas and discusses specific genetic findings that may explain reported benefits from immunotherapy.A correction to this article is available online at https://doi.org/10.1186/s40425-019-0792-9.Abbreviations:ASangiosarcomaCGPcomprehensive genomic profilingCRcomplete responseFPKMfragments per Kilobase per millionICIImmune checkpoint inhibitorsirAEimmune related adverse effectsMSImicrosatellite instabilityPBMCperipheral mononuclear cellsRNA-SeqRNA sequencingT regsT regulatory cellsTCGAThe Cancer Genome AtlasTILstumor infiltrating lymphocytesTMBtumor mutation burdenWESwhole exome sequencing