Neoadjuvant Pimicotinib Combined With Surgery Versus Upfront Surgery for Diffuse Tenosynovial Giant Cell Tumor

Summary

Tenosynovial giant cell tumor (TGCT) is a rare neoplasm predominantly occurring in young and middle-aged adults, characterized by high recurrence and high disability rates. Surgery represents the first-line treatment at present. Although surgical resection can eradicate lesions, repeated surgical interventions constitute the major disease-related burden. Particularly for patients with diffuse-type TGCT (D-TGCT), postoperative recurrence rates can exceed 50%. Pimicotinib is a highly selective colony-stimulating factor 1 receptor (CSF1R) inhibitor. The phase III MANEUVER trial has verified its prominent tumor shrinkage effect and symptomatic improvement in patients with unresectable, symptomatic TGCT, with an objective response rate (ORR) of 54%. In addition, pimicotinib demonstrates a favorable safety profile; most adverse events are mild in severity, mainly including pruritus, edema, fatigue and elevated creatine kinase, without severe hepatotoxicity. Neoadjuvant therapy followed by surgery falls within the scope of multimodal treatment, which is mostly applied to recurrent and refractory cases rather than the standard upfront regimen for treatment-naive patients. Clinical case reports and real-world observations have preliminarily validated the feasibility and clinical value of sequential systemic targeted therapy followed by surgical resection. To date, systematic and standardized clinical data regarding neoadjuvant strategies remain scarce, especially randomized controlled evidence comparing neoadjuvant targeted therapy plus surgery versus primary upfront surgery. This study aims to compare the efficacy and safety of neoadjuvant pimicotinib combined with surgery versus upfront primary surgery in the management of D-TGCT, so as to generate evidence-based rationale for developing more effective and safe therapeutic regimens for D-TGCT.

Timeline

Start

2027-10-01

Primary completion

2029-09-30

Completion

2030-09-30

Publications

• Background Xu H, Niu X, Ravi V, Martin-Broto J, Razak AA, Saleh R, Zhou Y, Shen J, Liu T, Sankhala KK, Serrano C, Stacchiotti S, Wang J, Baldi GG, Feng Y, Hua Y, Li T, Rutkowski P, Zhang X, Tinoco G, Zou Q, Shan B, Zhu X, Gelderblom H. Pimicotinib versus placebo for tenosynovial giant cell tumour (MANEUVER): an international, randomised, placebo-controlled, phase 3 trial. Lancet. 2026 Mar 14;407(10533):1072-1083. doi: 10.1016/S0140-6736(25)02602-9. Epub 2026 Mar 5.
• Background van de Sande M, Blay JY, Tap W, Lee M, Kaiser E, Beaver S, Harrow B, Zeringo NA, Bernthal N. The economic and humanistic burden of tenosynovial giant cell tumor: a targeted literature review. Future Oncol. 2025 Aug;21(18):2385-2400. doi: 10.1080/14796694.2025.2520744. Epub 2025 Jun 22.
• Background Tap WD, Gelderblom H, Palmerini E, Desai J, Bauer S, Blay JY, Alcindor T, Ganjoo K, Martin-Broto J, Ryan CW, Thomas DM, Peterfy C, Healey JH, van de Sande M, Gelhorn HL, Shuster DE, Wang Q, Yver A, Hsu HH, Lin PS, Tong-Starksen S, Stacchiotti S, Wagner AJ; ENLIVEN investigators. Pexidartinib versus placebo for advanced tenosynovial giant cell tumour (ENLIVEN): a randomised phase 3 trial. Lancet. 2019 Aug 10;394(10197):478-487. doi: 10.1016/S0140-6736(19)30764-0. Epub 2019 Jun 19.
• Background Stacchiotti S, Durr HR, Schaefer IM, Woertler K, Haas R, Trama A, Caraceni A, Bajpai J, Baldi GG, Bernthal N, Blay JY, Boye K, Broto JM, Chen WT, Dei Tos PA, Desai J, Emhofer S, Eriksson M, Gronchi A, Gelderblom H, Hardes J, Hartmann W, Healey J, Italiano A, Jones RL, Kawai A, Leithner A, Loong H, Mascard E, Morosi C, Otten N, Palmerini E, Patel SR, Reichardt P, Rubin B, Rutkowski P, Sangalli C, Schuster K, Seddon BM, Shkodra M, Staals EL, Tap W, van de Rijn M, van Langevelde K, Vanhoenacker FMM, Wagner A, Wiltink L, Stern S, Van de Sande VM, Bauer S. Best clinical management of tenosynovial giant cell tumour (TGCT): A consensus paper from the community of experts. Cancer Treat Rev. 2023 Jan;112:102491. doi: 10.1016/j.ctrv.2022.102491. Epub 2022 Dec 6.
• Background Mosher H, Dean K, Meli G, Desrosiers J, Crawford B, Temple HT, Hornicek FJ, Rosenberg AE, Jonczak E, Palmerini E, Geiger EJ. Current Treatment Strategies for Diffuse Tenosynovial Giant Cell Tumor: A Review of the Literature. JB JS Open Access. 2026 Jan 13;11(1):e25.00313. doi: 10.2106/JBJS.OA.25.00313. eCollection 2026 Jan-Mar.
• Background Mastboom MJL, Lips W, van Langevelde K, Mifsud M, Ng C, McCarthy CL, Athanasou NA, Gibbons CLMH, van de Sande MAJ. The effect of Imatinib Mesylate in diffuse-type Tenosynovial Giant Cell Tumours on MR imaging and PET-CT. Surg Oncol. 2020 Dec;35:261-267. doi: 10.1016/j.suronc.2020.08.030. Epub 2020 Aug 26.
• Background Gelderblom H, Bhadri V, Stacchiotti S, Bauer S, Wagner AJ, van de Sande M, Bernthal NM, Lopez Pousa A, Razak AA, Italiano A, Ahmed M, Le Cesne A, Tinoco G, Boye K, Martin-Broto J, Palmerini E, Tafuto S, Pratap S, Powers BC, Reichardt P, Casado Herraez A, Rutkowski P, Tait C, Zarins F, Harrow B, Sharma MG, Ruiz-Soto R, Sherman ML, Blay JY, Tap WD; MOTION investigators. Vimseltinib versus placebo for tenosynovial giant cell tumour (MOTION): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2024 Jun 22;403(10445):2709-2719. doi: 10.1016/S0140-6736(24)00885-7. Epub 2024 Jun 3.
• Background Geiger EJ, Jensen AR, Singh AS, Nelson SD, Bernthal NM. Use of neoadjuvant pexidartinib with limb salvage surgery for diffuse tenosynovial giant cell tumor: A case report. J Orthop Sci. 2024 Jan;29(1):458-462. doi: 10.1016/j.jos.2022.10.016. Epub 2022 Nov 16. No abstract available.
• Background Bernthal NM, Spierenburg G, Healey JH, Palmerini E, Bauer S; TOPP Study Group; Gelderblom H, Staals EL, Lopez-Bastida J, Fronk EM, Ye X, Laeis P, van de Sande MAJ. The diffuse-type tenosynovial giant cell tumor (dt-TGCT) patient journey: a prospective multicenter study. Orphanet J Rare Dis. 2021 Apr 29;16(1):191. doi: 10.1186/s13023-021-01820-6.
• Background Bernthal NM, Randall RL, Zeitlinger LN, Geiger EJ, Healey JH. Complementary Effects of Surgery and Pexidartinib in the Management of Patients with Complex Diffuse-Tenosynovial Giant Cell Tumor. Case Rep Orthop. 2022 Dec 3;2022:7768764. doi: 10.1155/2022/7768764. eCollection 2022.

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