Although taxanes (TAX) are effective for advanced cutaneous angiosarcoma (CAS) and stand as a current first-line treatment, no standardized second-line treatment has yet been established. Eribulin methylate (ERB), a non-taxane microtubule inhibitor, improved the overall survival (OS) of patients with advanced sarcoma compared to dacarbazine in a randomized, phase 3 trial. Based on this study, ERB was approved to use for all types of sarcoma in Japan. We hypothesized that ERB would be most active in patients with TAX-resistant CAS as both TAX and ERB target microtubules but through different mechanisms.
We designed a single-arm, prospective observational study of ERB administered at a dose of 1.4mg/m2 on days 1 and 8 in a 21-day cycle. Advanced, TAX-resistant CAS patients scheduled for ERB use were enrolled. The primary endpoint was OS and the secondary endpoints were response ratio (RR), progression-free survival (PFS), and toxicity assessment.
The last patient was enrolled in January 2018 and the data was locked at the end of March 2019. In total, 25 patients with CAS (median age 74) were enrolled. All patients had prior TAX exposure and 5 patients had 2 or more prior therapy courses. All patients except 1 had their primary tumours in the head and neck while 10 patients had distant metastasis. Performance status (PS) was generally good; 14 were PS0, 8 were PS1, and 3 were PS2. The median follow-up period was 250 (16-849) days. The rate of OS and PFS at 6 months estimated by Kaplan-Meier method was 67% and 24%, respectively. Median OS and PFS were 8.6 and 3.0 months, respectively. RR at week 7, 13, and 25 were 24% (6/25), 16.7% (4/25) and 13% (3/23), respectively. Although 10 patients experienced severe toxicity (8 had neutropenia, 2 had anemia and 1 had a retroperitoneal abscess), they all recovered.
ERB showed a promising and durable response and was well-tolerated in TAX-resistant CAS. Both RR and OS were comparable to previous results where ANGIOTAX was used as a second-line treatment. The most common toxicity was neutropenia but this was manageable. Taken together, this study provides evidence to support ERB use in TAX-resistant CAS cases.
UMIN000023331.
The authors.
Maruho Takagi Dermatology Foundation.
All authors have declared no conflicts of interest.