Fujisawa Y, Fujimura T, Matsushita S, Yamamoto Y, Uchi H, Otsuka A, Funakoshi T, Miyagi T, Hata H, Gosho M, Kambayashi Y, Aoki M, Yanagi T, Ohira A, Nakamura Y, Maeda T, Yoshino K
Dermatology Division, University of Tsukuba, Tsukuba, Japan.
Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, Japan.
Br J Dermatol. 2020 Nov;183(5):831-839. doi: 10.1111/bjd.19042. Epub 2020 May 26.
Taxanes are the current first-line treatment for advanced cutaneous angiosarcoma (CAS) for patients who are considered difficult to treat with doxorubicin owing to advanced age or comorbidity. However, no effective second-line therapy for such patients has been established.
We designed a single-arm prospective observational study of eribulin mesylate (ERB) administered at a dose of 1·4 mg m on days 1 and 8 in a 21-day cycle. Patients with advanced CAS who were previously treated with a taxane and were scheduled to begin ERB treatment were enrolled. The primary endpoint was overall survival (OS) and the secondary endpoints were response rate (RR), progression-free survival (PFS) and toxicity assessment.
We enrolled a total of 25 patients. The median OS and PFS were 8·6 months and 3·0 months, respectively. The best overall RR was 20% (five of 25). In total, 16 grade 3/4 severe adverse events (SAEs) occurred; however, all patients recovered. Patients who achieved partial response or stable disease as best response had longer OS than those with progressive disease (median OS not reached and 3·3 months, respectively; P < 0·001). Patients who did not experience SAEs showed longer OS than those who did (median OS 18·8 months and 7·5 months, respectively; P < 0·05). Patients with distant metastasis had shorter median OS than those with locoregional disease, but without statistically significant difference.
ERB showed a promising RR and is a potential candidate for second-line treatment for patients with CAS, after treatment with taxanes. However, owing to the occurrence of SAEs in over half of the participants, caution should be exercised regarding ERB use in elderly patients. What is already known about this topic? Taxanes are the current first-line treatment for patients with advanced cutaneous angiosarcoma (CAS) who are considered difficult to treat with doxorubicin owing to advanced age or comorbidity. No effective therapy for taxane-resistant CAS has been established thus far. Eribulin suppresses microtubule polymerization and elicits an antitumour effect similar to that of taxanes. What does this study add? In our single-arm prospective observational study to evaluate the efficacy of eribulin for treating patients with advanced CAS who previously received taxanes, the median overall survival and progression-free survival were 8·6 and 3·0 months, respectively. Response rates at weeks 7, 13 and 25 were 20%, 17% and 14%, respectively. Although 16 grade 3/4 severe adverse events occurred, all patients recovered. Eribulin showed a promising response rate and is a potential candidate for second-line treatment in CAS after taxane treatment. Linked Comment: Smrke and Benson. Br J Dermatol 2020; 183:797-798.
对于因年龄较大或合并症而被认为难以用阿霉素治疗的晚期皮肤血管肉瘤（CAS）患者，紫杉烷类药物是目前的一线治疗方法。然而，尚未确立针对此类患者的有效二线治疗方案。
我们设计了一项单臂前瞻性观察性研究，使用甲磺酸艾瑞布林（ERB），剂量为1.4mg/m²，在第1天和第8天给药，每21天为一个周期。纳入先前接受过紫杉烷类药物治疗且计划开始ERB治疗的晚期CAS患者。主要终点是总生存期（OS），次要终点是缓解率（RR）、无进展生存期（PFS）和毒性评估。
我们共纳入25例患者。中位OS和PFS分别为8.6个月和3.0个月。最佳总RR为20%（25例中的5例）。总共发生了16例3/4级严重不良事件（SAEs）；然而，所有患者均康复。达到部分缓解或疾病稳定作为最佳缓解的患者的OS长于疾病进展的患者（中位OS分别未达到和3.3个月；P<0.001）。未发生SAEs的患者的OS长于发生SAEs的患者（中位OS分别为18.8个月和7.5个月；P<0.05）。远处转移患者的中位OS短于局部区域疾病患者，但无统计学显著差异。
ERB显示出有前景的RR，是紫杉烷类药物治疗后CAS患者二线治疗的潜在候选药物。然而，由于超过一半的参与者发生了SAEs，在老年患者中使用ERB时应谨慎。关于该主题已知的信息有哪些？对于因年龄较大或合并症而被认为难以用阿霉素治疗的晚期皮肤血管肉瘤（CAS）患者，紫杉烷类药物是目前的一线治疗方法。迄今为止，尚未确立针对紫杉烷耐药CAS的有效治疗方法。艾瑞布林抑制微管聚合并引发与紫杉烷类药物类似的抗肿瘤作用。本研究增加了什么内容？在我们评估艾瑞布林治疗先前接受过紫杉烷类药物治疗的晚期CAS患者疗效的单臂前瞻性观察性研究中，中位总生存期和无进展生存期分别为8.6个月和3.0个月。第7、13和25周的缓解率分别为20%、17%和14%。虽然发生了16例3/4级严重不良事件，但所有患者均康复。艾瑞布林显示出有前景的缓解率，是紫杉烷类药物治疗后CAS二线治疗的潜在候选药物。相关评论：Smrke和Benson。《英国皮肤病学杂志》2020年；183:797 - 798。
