Malignant Solitary Fibrous Tumours Show Pazopanib Response

Patients with metastatic or unresectable malignant solitary fibrous tumours might benefit from treatment with the anti-angiogenic agent pazopanib

medwireNews: Preliminary results suggest that the vascular endothelial growth factor–tyrosine kinase inhibitor pazopanib may be active against advanced malignant or dedifferentiated solitary fibrous tumours. 

The phase II study published in The Lancet Oncology details the outcome of 36 patients with metastatic or unresectable solitary fibrous tumours, 34 of whom had malignant disease and two who had dedifferentiated tumours. 

The patients completed a median 5.5 cycles of pazopanib 800 mg/day until disease progression or intolerance, during which time 58% required dose interruption and 28% required dose reductions, report Javier Martin-Broto, from Instituto de Biomedicina de Sevilla in Spain, and co-authors. 

Using the Choi criteria, 51% of the patients experienced a partial tumour response, 26% had stable disease and 23% disease progression.  

Overall survival at 2 years was 73% and the median value is yet unreached, while median progression-free survival was 8.47 months for patients who responded to treatment versus 3.53 months for those who did not, a significant difference. 

These values seem to “compare favourably to historical controls with solitary fibrous tumour treated with chemotherapy”, and provide a “benchmark for future trials”, the investigators write. 

Multivariate analysis suggested that overexpression of the ubiquitin-like protein gene ISG15 was associated with a significantly greater likelihood of disease progression and death, with hazard ratios of 6.61 and 10.73, respectively. 

The prognostic role of ISG15 and BCL2 – overexpression of which was also linked to patient outcome in univariate analysis – “will be functionally validated and comparatively analysed with the typical solitary fibrous tumour cohort once accrual has been completed”, Javier Martin-Broto et al say. 

Of concern, enrolment of patients with dedifferentiated solitary fibrous tumours was terminated as planned interim analysis suggested early and fast progression among the two patients in this subgroup, at 0.57 and 1.73 months, respectively. 

Nevertheless, there were no adverse event-related fatalities in the study. The most common grade 3 or more/higher/worse severe adverse events were hypertension (31%), neutropenia (11%) and elevations in alanine aminotransferase (11%) and bilirubin (8%). 

“The manageable toxicity profile and the activity shown by pazopanib suggests that this drug could be an option for systemic treatment of advanced malignant solitary fibrous tumour”, the investigators conclude. 



Martin-Broto J, Stacchiotti S, Lopez-Pousa A, et al. Pazopanib for treatment of advanced malignant and dedifferentiated solitary fibrous tumour: a multicent re , single-arm, phase 2 trial . Lancet Oncol; Advance online publication 18 December 2018.

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