Taxanes (TAX) are the current first-line treatment for advanced cutaneous angiosarcoma (CAS). On the other hand, eribulin (ERB) is a nontaxane microtubule inhibitor approved for treatment of advanced sarcoma in Japan. However, no study has evaluated ERB in CAS patients. We hypothesized that ERB would be well tolerated and active in patients with TAX-resistant CAS because TAX and ERB have different mechanisms of action to inhibit microtubule formation.
We designed a single-arm, prospective observational study of ERB administered at dose of 1.4 mg/m2 on days 1 and 8 in every 21 days. TAX-resistant, advanced CAS patients for whom ERB use was planned were enrolled. The primary endpoint is overall survial (OS), and the secondary endpoint, response ratio (RR), progression-free survival (PFS), and toxicity assessment. The estimated median OS in a previous clinical study (ANGIOTAX), in which patients received TAX as the second-line treatment, was 6 months, so we set this number as the threshold and expected a 6-month OS of 70% with ERB treatment. Based on these numbers, the required number of patients to be enrolled was calculated as 31; thus, we set 35 patients as the target number.
At the time of submissiion, 25 CAS patients, median age 74, were enrolled. All had prior TAX exposure. In all but 1 patient the primary tumor was in the head and neck, and 10 patients had a metastatic tumor. The performance status (PS) was generally good: 22 with PS0 or 1. The median follow-up period was 161 (47-464) days. The respective Kaplan-Meier estimates for OS and PFS rates at 6 months were 70% and 31%. The respective median OS and PFS were not-reached and 94 days. The respective RR at weeks 7, 13, and 25 were 24%, 12% and 11%. No death related to treatment was observed. Although 9 patients experienced >grade 3 toxicity (7, neutropenia; 2, anemia; 1, retroperitoneal abscess), they all recovered.
ERB is a well-tolerated regimen with promising activity in TAX-resistant CAS. The common toxicity is neutropenia, which requires growth factor support. This study is underway and enrollment is expected to be completed in 2018. This study may provide a new treatment option for patients with PTX-resistant CAS.
Clinical trial identification
Legal entity responsible for the study
University of Tsukuba.
Has not received any funding.
All authors have declared no conflicts of interest.