Advertisement Commentary|Videos|May 11, 2026 Dr Randall on the Rationale for Investigating CSF-1R Inhibition in TGCT Author(s)R. Lor Randall, MD, FACS Fact checked by: Courtney Flaherty, Caroline Seymour R. Lor Randall, MD, FACS discusses safety and efficacy data from the MANEUVER trial, which evaluated pimicotinib in TGCT. Advertisement “One of the most important recent developments is that, in select tumors, we are now able to meaningfully alter disease biology and patient function with targeted systemic therapy beyond the operating room.”R. Lor Randall, MD, FACS, the David Linn Endowed Chair for Orthopedic Surgery, the chair of the Department of Orthopedic Surgery, and a professor at UC Davis Comprehensive Cancer Center, discusses the clinical rationale for evaluating selective CSF-1R inhibition with pimicotinib (ABSK021) in tenosynovial giant cell tumors (TGCT).Randall explained that while orthopedic oncology has historically been defined by surgical intervention, recent advancements allow clinicians to meaningfully alter disease biology and patient function using targeted systemic therapy beyond the operating room. This shift is particularly relevant in TGCT, where the disease, while not a high-grade sarcoma, presents as a locally aggressive and destructive process that can severely impact joints.The clinical challenge of TGCT lies in its tendency to cause associated pain, stiffness, and profound functional limitations for patients. Randall noted that the diffuse variant of the disease is distinct from the nodular variant and is notoriously difficult to manage. Complete surgical resection of the diffuse type is often unfeasible, which results in high recurrence rates. Consequently, patients are frequently subjected to repeated operations that can lead to progressive joint damage and cumulative morbidity. This cycle of recurrence and re-operation has created a clear unmet need for systemic therapies that can palliate symptoms and stabilize the disease without further surgical trauma.To address this, investigators conducted the phase 3 MANEUVER trial (NCT05804045). This randomized, double-blind, placebo-controlled study evaluated pimicotinib, a highly selective oral CSF-1R inhibitor, in patients with symptomatic TGCT for whom surgery was not recommended due to anticipated morbidity or functional compromise.By targeting the underlying biology of the tumor, these systemic options aim to provide a therapeutic bridge for patients who would otherwise face limited options. Ultimately, Randall emphasized that this research is vital for medical oncologists to understand, as it marks a transition in the specialty toward incorporating precision medicine into the treatment of locally aggressive bone and soft tissue tumors.Hear more from Dr Randall about this trial in the following Q&A article. NewsletterStay up to date on the most recent and practice-changing oncology dataSubscribe Now! Advertisement Related ContentAdvertisementDr Randall on Long-Term Responses and Functional Benefits With Pimicotinib in TGCTByR. 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