Emactuzumab Therapy Shows Promise for Soft Tissue Giant Cell Tumours

Targeted therapy shows potential for patients with benign, giant cell soft tissue tumours

medwireNews: Phase I trial results suggest that monoclonal antibody therapy may be feasible for patients with diffuse-type tenosynovial giant cell tumours(dt-GCT) of the soft tissue.

dt-GCT, also known as pigmented villonodular synovitis, are characterised by a chromosomal translocation leading to overexpression of colony-stimulating factor (CSF)1; recruitment of macrophages with the CSF1 receptor results in the formation of multinucleated giant cells.

Emactuzumab, which inhibits CSF1,was tested in 12 patients at a dose of 900 mg, 1350 mg or 2000 mg every 2 weeks for the dose-escalation arm of the first trial to test the agent in humans.

No dose-limiting toxicities were recorded and a further 17 patients were treated with a 1000 mg dose every 2 weeks, report Antoine Italiano, from Institut Bergonié in Bordeaux, France, and co-investigators.

Safety data available for a total of 25 individuals showed that the most common side effects were grade 1 or 2 facial oedema (64%), asthenia (56%) and pruritus (56%).

Five patients experienced serious grade 2 or 3 events, all but one of which were at doses above 1000 mg, and these included two cases of lupus erythematosus and one case each of erythema, periorbital oedema and dermohypodermitis. In addition, one patient experienced grade 3 mucositis and another grade 3 fatigue.

Pharmacokinetic analysis revealed tumour shrinkage in 27 patients given doses of 900 mg to 2000 mg that was associated with “early profound functional and symptomatic improvement”, the team writes in The Lancet Oncology.

An objective response was achieved by 86% of 28 patients, with a complete response in 7% and a partial response in 79%. A partial response was achieved by 68% of patients within three cycles of treatment.

“Even a short course of emactuzumab could offer durable benefit for patients for whom surgery is either not feasible or would result in major functional impairment”, say the authors.

“Further investigation of emactuzumab in dt-GCT is warranted and, in view of the rarity of the disease, different possibilities such as an international collaboration with cooperative groups are being assessed.”

David Thomas, from the Garvan Institute of Medical Research in Sydney, New South Wales, Australia, writes in a comment that the emergence of systemic agents for benign, non-lethal tumours raises questions on the optimal duration of treatment and long-term consequences.

“A specific issue for younger patients is reproductive decision-making, because we do not know the effects on the developing foetus of these targeted therapies”, he observes.

“Another interesting issue to consider is the effect of administering new treatments on specialist connective tissue tumour services, because of the duration of treatment and because it is difficult to predict the numbers of benign tumours that might be increasingly referred for therapy.”


Cassier PA, Italiano A, Gomez-Roca CA, et al. CSF1R inhibitionwith emactuzumab in locally advanced diffuse-type tenosynovial giant cell tumours of the soft tissue: a dose-escalation and dose-expansion phase 1 study. Lancet Oncol; Advance online publication 12 July 2015. doi:10.1016/S1470-2045(15)00132-1

Thomas DM. The growing problem of benign connective tissue tumours. Lancet Oncol; Advance online publication 12 July 2015. doi:10.1016/S1470-2045(15)00147-3

medwireNews (www.medwireNews.com ) is an independent medical news service provided by Springer Healthcare Limited.© Springer Healthcare Ltd; 2015