Skin angiosarcoma is a rare cancer caused by the canceration of cells inside blood vessels (vascular endothelial cells), with a 5-year survival rate of less than 10 %. The number of patients in Japan is higher than in Europe and the United States (2.5 per million), and the incidence rate has been increasing in recent years. The overall survival rate for first-line treatment of skin angiosarcoma is short (649 days), and it is difficult to achieve long-term remission with first-line treatment alone. In addition, the majority of patients experience serious adverse events even with second-line treatment, so the development of new treatments is urgently needed.

Current Treatments and Challenges

Angiosarcoma is a rare cancer with an incidence rate of approximately 2-3% of sarcomas and increasing in recent years. The target organs are reported to be highest in the skin (49.6%), followed by breast parenchyma (14.4%), soft tissue (11.2%), heart (6.7%), bone (4.1%), and others (14.0%). Previously, the skin accounted for about one-third of cases, but in recent years, it has increased to about one-half, and the increase in cutaneous angiosarcomas occurring after radiation therapy is thought to be the cause.

Current treatment for angiosarcoma is a combination of immunotherapy, surgery, radiation therapy, and chemotherapy, but the prognosis is extremely poor. The first-choice drug for angiosarcoma is the taxane anti-cancer drug (paclitaxel), an apoptosis inducer, but the overall survival rate with paclitaxel is short (649 days), making it difficult to achieve long-term remission. In addition, the median administration period of paclitaxel as maintenance therapy is only 274 days, which is not satisfactory. Therefore, in the treatment of angiosarcoma, treatment after the second line is important, but the response rate of eribulin and pazopanib, which are used as second line treatments, is 15-20 %, and the majority of patients experience serious adverse events.

There is no effective treatment for the second line treatment, which is important in the treatment of angiosarcoma, and the development of new effective and safe treatments is urgently needed.

Characteristics of Our Solution

PAI-1 is expressed on vascular endothelial cells, and its tumor, angiosarcoma, also expresses high levels of PAI-1. It has been reported that patients with high expression of PAI-1 are less likely to respond to paclitaxel in first-line treatment. Paclitaxel induce apoptosis, a type of cell death in angiosarcoma, but cancer cells that express high levels of PAI-1 are less likely to undergo apoptosis. The combination of paclitaxel and the PAI-1 inhibitor RS5614 may enhance the therapeutic effect of paclitaxel on angiosarcoma.

In collaboration with Tohoku University, a Phase II investigator-initiated clinical trial is being conducted to evaluate the efficacy and safety of the combination of paclitaxel and RS5614 in patients with cutaneous angiosarcoma who are refractory to paclitaxel.

Progress to date

In October 2023, in collaboration with domestic university hospitals such as Tohoku University, Jichi Medical University, Kyushu University, Nagoya City University, National Cancer Center Hospital, and Cancer Research Institute Ariake Hospital, a phase II investigator-initiated clinical trial to evaluate the efficacy and safety of the combination of paclitaxel and RS5614 in 16 patients with cutaneous angiosarcoma, in whom the taxane anticancer drug paclitaxel had failed, was started. If the efficacy can be verified in this study, a new treatment method can be proposed for patients with cutaneous angiosarcoma for which there are no effective treatments.