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

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.

Conflict of interest statement

Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Peter Grimison, Christine Chevreau, Sophie Piperno-Neumann, Axel Le Cesne, Virginia Ferraresi, Antoine Italiano, Florence Duffaud, Nicolas Penel, Severine Metzger, Sylvia Chabaud, Lizz van der Heijden, Jean-Yves Blay, Hans Gelderblom declare no conflict of interest within the present study. Silvia Stacchiotti has no conflict of interest to declare within the present study; she reports institutional research funding from Amgen Dompe, Advenchen, Bayer, Blueprint Medicines, Deciphera, Eli Lilly, Epizyme, Daiichi Sankyo Pharma, GSK, Karyopharm, Novartis, Pfizer, PharmaMar, SpringWorks, and Hutchinson MediPharma International Inc; honoraria from Bayer, Deciphera, Eli Lilly, Daiichi, Maxivax, and Novartis; invited speaker fees/meeting support from GSK and PharmaMar; fees for expert testimony from Bavarian Nordic and Epizyme; and participation on a Data Safety Monitoring Board or Advisory Board for Bayer, Deciphera, Eli Lilly, Daiichi, Maxivax, and Novartis outside the submitted work. Geert Spierenburg and Michiel van de Sande report institutional research funding from Daichii-Sankyo outside the submitted work. David Perol received personal fees from AstraZeneca, Bayer, Boehringher-Ingelheim, Bristol Myers Squibb, Eli-Lilly, Ipsen, Roche, Novartis, Merck Sharp and Dohme, Takeda.

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