Treatment Beyond Progressive Disease With Pazopanib for Cutaneous Angiosarcoma: A Case Report

Cutaneous angiosarcoma (CAS) is a highly malignant vascular tumor, often in the head and neck of elderly patients. For tumors > 5 cm, taxane-based chemoradiotherapy using paclitaxel or docetaxel is considered standard treatment, although weekly paclitaxel achieved a median progression-free survival (PFS) of approximately 4 months 1. The oral multi-targeted tyrosine kinase inhibitor pazopanib has recently been used after taxane failure. Pazopanib blocks vascular endothelial growth factor receptors, platelet-derived growth factor receptors, and c-Kit, resulting in the inhibition of angiogenesis and promotion of cytostatic effects 2. Our case of CAS was successfully controlled for 4 years with pazopanib, indicating its potential role in prolonged survival, suggesting a potential role for sustained treatment beyond disease progression. A woman in her 60s developed erythematous, infiltrative patches on the left forehead and right temporal region 2 months before her first visit (Figure 1A–C). Biopsy revealed CD31, ERG, and D2-40 positive cells, and Ki-67 labeling index of 40%. CAS without distant metastases was diagnosed (Figure 1D–G). She underwent electron beam irradiation (70 Gy) followed by weekly paclitaxel (60 mg/m2 on days 1, 8, and 15 per 4-week cycle), which was discontinued after 3 months because of neuropathy. Complete response (CR) was achieved. Oral pazopanib 800 mg/day was started to maintain CR, and grade 2 hepatic dysfunction at week 4 prompted a reduction to 400 mg/day, later alternating with 200 mg because of fatigue. At 13 months, a new forehead rash appeared (Figure 1H) and was pathologically confirmed as CAS. The dose was increased to 400 mg/day according to the patient's preference. The lesion grew slowly without distant spread. Parotid gland metastasis occurred at 26 months (Figure 1I), but treatment continued. At 35 months, local progression prompted re-escalation to 800 mg/day with good tolerance for ~1 year (Figure 1J). Lung metastases emerged at 4 years (Figure 1K,L), leading to a switch to eribulin. Disease control failed, and the patient died. Treatment options for CAS become limited after discontinuation of taxane-based agents. Conversely, the continued use of a therapeutic agent after disease progression is referred to as treatment beyond progressive disease (PD), implying that ongoing therapy may provide clinical benefit despite the absence of objective tumor responses 3. Evidence regarding the use of pazopanib for treatment beyond PD in CAS remains scarce. Ogata et al. reported a median PFS of 94 days following pazopanib treatment in patients with taxane-resistant CAS 4. Watanabe et al. reported 15 months of disease stabilization 5. To the best of our knowledge, this case represents the longest uninterrupted course of pazopanib administration in CAS, lasting 4 years despite local recurrence and metastasis. Although an inherently indolent course cannot be excluded, CAS rarely behaves in this manner. Therefore, the prolonged survival of our patient suggests that continued multi-kinase inhibition beyond PD may have contributed to suppression of rapid tumor acceleration. In addition, acceptable tolerability over long-term administration indicates that this approach may be feasible in carefully selected elderly patients. Prospective studies should determine whether treatment beyond PD prolongs overall survival in CAS. We thank J. Ludovic Croxford, PhD, from Edanz (https://jp.edanz.com/ac) for editing a draft of this manuscript. The authors have nothing to report. The authors have nothing to report. The patient whose data were reported in this manuscript has given written informed consent to publish the case details. The authors declare no conflicts of interest. Yumi Aoyama is an Editorial Board member of Journal of Dermatology and a co-author of this article. To minimize bias, they were excluded from all editorial decision-making related to the acceptance of this article for publication. The data that support the findings of this study are available from the corresponding author upon reasonable request.