Nilotinib Shows Promise For Pigmented Villonodular Synovitis

Phase II trial findings suggest nilotinib may have anti-tumour activity against locally advanced pigmented villonodular synovitis

medwireNews: The oral tyrosine kinase inhibitor nilotinib may offer a novel treatment for patients with locally advanced pigmented villonodular synovitis, suggest 12-week disease control findings from a phase II trial.

The rare disease, also known as diffuse-type giant cell tumour, is driven by a gene translocation resulting in overexpression of colony-stimulating factor (CSF)1, explain Jean-Yves Blay, from University Claude Bernard Lyon in France, and colleagues.

Following preliminary research pointing to a potential role for the chronic myeloid leukaemia agent nilotinib, which is known to inhibit the CSF1 receptor, the researchers recruited 56 patients with progressive or relapsing disease that was inoperable or resectable only with mutilating surgery.

Patients were assigned to use nilotinib 400 mg twice daily for up to 1 year; the median duration of treatment was 11.0 months, with 55% completing the year and six patients continuing to use nilotinib for up to 22 months.

The mean Bayesian-estimated proportion of patients who completed at least 3 weeks of treatment, underwent imaging at week 12 and were free from disease progression at this timepoint was 92.6%, the team reports in The Lancet Oncology.

Stable disease was achieved in 90% of 51 evaluable patients, while partial responses were recorded in 6% and lasted between 40 and 52 months. There were no patient deaths.

However, Francois Gouin, from the University Hospital of Nantes in France, points out in a linked comment that the disease progression of pigmented villonodular synovitis is “highly heterogeneous” with many patients experiencing stable residual disease after surgery.

“A controlled trial is necessary to assess the effect of disease control using targeted therapies more accurately over the natural history of the disease”, he writes.

Five patients discontinued nilotinib before the initial 12 weeks including three who stopped treatment within 6 weeks because of side effects, namely grade 2 hypotension, grade 2 limb oedema and grade 3 headache.

Indeed, 96% of the 56 participants experienced at least one treatment-related adverse event and 11% had at least one grade 3 or more severe event including headache, dizziness and hepatic disorders in one patient, pruritus and toxidermia in another, while diarrhoea, elevated gamma-glutamyltransferase, anorexia, and increased headache all occurred in one patient each.

Nevertheless, there were no grade 4 or 5 events and the researchers describe the toxicity as “manageable”, recommending that the side effect profile of nilotinib be compared against that of alternative treatments and surgery-related morbidity, including amputation in some cases.

“In view of the paucity of available therapies for patients with progressive or relapsing pigmented villonodular synovitis, the efficacy of nilotinib or other drugs that target [the CSF1 receptor] in this disease needs to be assessed in randomised trials”, Jean-Yves Blay and co-authors conclude.

Commentator Francois Gouin emphasizes that as the tumour is rarely fatal, future trial endpoints should include impact of treatment on clinical symptoms, side effects of medical treatment, and the functional impact of surgery and complications on quality of life.

“Oncological and functional specialists, such as orthopaedic surgeons and rheumatologists, should pool their skills to accurately define the targeted populations eligible for combined treatment, to define appropriate outcome scores, and to establish relevant therapeutic strategies, to improve the condition and outcomes of patients with recurrent, progressive, and disabling forms of pigmented villonodular synovitis”, he summarises.


Gelderblom H, Cropet C, Chevreau C, et al. Nilotinib in locally advanced pigmented villonodular synovitis: a multicentre, open-label, single-arm, phase 2 trial . Lancet Oncol; Advance online publication 20 March 2018. DOI:

Gouin F. Nilotinib in locally advanced pigmented villonodular synovitis: challenges of a new targeted therapy. Lancet Oncol; Advance online publication 20 March 2018. DOI:

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