Long-term follow-up of nilotinib in patients with advanced tenosynovial giant cell tumours: Long-term follow-up of nilotinib in TGCT

Eur J Cancer. 2022 Sep:173:219-228. doi: 10.1016/j.ejca.2022.06.028. Epub 2022 Aug 3.

Abstract

Background: Diffuse-type tenosynovial giant cell tumour (D-TGCT) is a non-malignant but locally aggressive tumour driven by overexpression of colony-stimulating factor-1 (CSF1). CSF1R inhibitors are potential therapeutic strategies for patients not amenable to surgery. We report here the long-term outcome of nilotinib in patients with advanced D-TGCT treated within a phase II prospective international study (ClinicalTrials.gov: NCT01261429).

Methods: Patients were enrolled between December 2010-September 2012 at 11 cancer centres. Eligible patients had histologically confirmed D-TGCT, not amenable to surgery. Patients received nilotinib until evidence of progression, toxicity or a maximum of one year. Long-term data were retrospectively collected after the completion of the phase II trial. Patients with nilotinib treatment ≥12 weeks and follow-up ≥12 months were included for long-term analysis.

Results: Forty-eight of 56 enrolled patients were included. Median treatment duration was 11 months; 31 (65%) patients completed the treatment protocol. After 102 months of follow-up (median; range 12-129), 25 patients (52%) had progression. The median progression-free survival (PFS) was 77 months. The five-year PFS rate was 53%. Fifteen patients (n = 15/46; 33%) experienced clinical worsening after 11 months (median). Twenty-seven patients (58%) received additional treatment, after which eleven patients (n = 11/27; 41%) had a second relapse. Nine patients required a subsequent treatment, primarily other CSF1R inhibitors (n = 6/9; 67%). No unfavourable long-term effects were observed.

Conclusion: This long-term analysis of nilotinib for advanced D-TGCT showed that about half of the patients had progression and underwent additional treatment after 8.5 years follow-up. Contrarily, several patients had ongoing disease control after limited treatment duration, demonstrating the mixed effect of nilotinib.

Keywords: CSF1; CSF1R inhibitor; Nilotinib; PVNS; TGCT; Tyrosine kinase inhibitor.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Follow-Up Studies
  • Giant Cell Tumor of Tendon Sheath* / drug therapy
  • Humans
  • Neoplasm Recurrence, Local / drug therapy
  • Prospective Studies
  • Pyrimidines
  • Retrospective Studies
  • Synovitis, Pigmented Villonodular* / drug therapy

Substances

  • Pyrimidines
  • nilotinib

Associated data

  • ClinicalTrials.gov/NCT01261429