Pazopanib shows promise as second-line option in rare cutaneous angiosarcoma

For patients with a rare and aggressive skin cancer, treatment options can quickly run out. New research suggests that pazopanib may offer a potential second-line option. In a single-arm confirmatory trial conducted in Japan, investigators found that while pazopanib did not meet its primary end point of improving progression-free survival (PFS), it showed higher-than-expected response rates and overall survival (OS), with no new safety concerns. The study was published last month in the British Journal of Dermatology.

Pazopanib, available as the brand Votrient and as a generic drug, is an oral tyrosine kinase inhibitor initially approved in 2009 for renal cell carcinoma and later for previously treated advanced soft-tissue sarcoma.

Cutaneous angiosarcomas are malignant vascular tumors of the skin that most often arise on the face and scalp, accounting for approximately 60% of all angiosarcoma cases. The aggressive disease most often affects older adults and is known for its poor prognosis, particularly in advanced stages. Paclitaxel chemotherapy has become the standard first-line treatment based on prior studies demonstrating meaningful activity, but there is no established second-line therapy for patients whose disease progresses or who cannot tolerate treatment. As a result, identifying effective follow-up options remains a significant unmet need.

To address this gap, investigators from the Japan Clinical Oncology Group, led by Kohei Oashi, M.D., Ph.D., conducted a clinical trial to evaluate pazopanib in this setting. The study enrolled 30 patients with paclitaxel-pretreated primary cutaneous angiosarcoma across 15 institutions in Japan.

Participants received oral pazopanib at a starting dose of 800 mg once daily. The primary point was PFS, with secondary end points including OS, response rate (RR), disease control rate and safety. Outcomes were compared against historical data from patients treated with second-line docetaxel following paclitaxel.

The results showed a median PFS of 2.8 months, which did not exceed the predefined threshold for success and was similar to the historical control of 2.7 months. However, other efficacy signals were more encouraging. Median OS reached 12.1 months, notably higher than historical benchmarks, and the objective response rate was 31.8%. The disease control rate, which includes patients with stable disease, was 63.6%.

Safety findings were consistent with the known profile of pazopanib. Most patients experienced nonhematologic adverse events, with 93.3% reporting grade 2 or higher events and 70% reporting grade 3 events. Common toxicities included high blood pressure and liver enzyme elevations. Importantly, no treatment-related deaths occurred, and investigators reported that adverse events were manageable with dose adjustments and monitoring.

The study population had a median age of 76 years, reflecting the older demographic typically affected by the disease. Investigators noted that starting pazopanib at the full 800 mg dose was feasible even in elderly patients, provided that clinicians carefully manage toxicity through dose reductions when needed.

Although the trial did not meet its primary end point, the authors emphasized that the favorable OS and response rates suggest meaningful clinical activity. “Our clinical hypothesis was not proven,” the researchers wrote. "However, considering that OS and RR tended to be better than expected and that there were no safety issues, pazopanib may be a treatment option.”

The findings also highlight the challenges of studying rare cancers. With limited patient populations and no standard second-line therapy for comparison, single-arm trials and historical controls are often necessary, though they come with inherent limitations. The authors noted that randomized trials would be ideal but are difficult to conduct in such a rare disease.

Still, the results position pazopanib as a viable consideration in clinical practice. Future research may focus on identifying which patients are most likely to benefit, as well as exploring combination strategies with immunotherapy or other targeted agents.

For now, this study adds important evidence to a sparse treatment landscape, offering clinicians another potential tool in managing a challenging and uncommon cancer.