Vimseltinib vs. pexidartinib: An indirect comparison of response rate in the treatment of tenosynovial giant cell tumor.

Abstract

e23567 Background: Tenosynovial giant cell tumor (TGCT) is a locally aggressive but rare neoplasm of the synovium, tendon sheaths, and bursae frequently affecting major joints with a mean age of diagnosis at 35 to 50 years. Surgical resection is the mainstay of treatment. While generally not life-threatening, inadequate treatment is associated with a significant decrease in quality of life. TGCT also overexpresses colony-stimulating factor I (CSF 1) which has been successfully targeted with an inhibitor, Pexidartinib, which has been the only systemic therapy available for TGCT not amenable to surgical resection. Vimseltinib is an overall switch control-tyrosine kinase inhibitor which does not have the associated hepatotoxicity of pexidartinib. No head-to-head clinical trial between these agents has been performed; this indirect treatment comparison seeks to establish their relative efficacy, by comparing rates of radiological response by RECIST criteria in their major trials. Methods: Data pertaining to the ENLIVEN (pexidartinib vs. placebo) and MOTION (vimseltinib vs. placebo) clinical trials was analyzed; overall response rates were extracted along with 95% confidence intervals. ENLIVEN was a phase 3 multinational randomized double-blind placebo controlled clinical trial with 1:1 randomization and MOTION was a phase 3 randomized double-blind placebo controlled clinical trial with 2:1 randomization. The placebo arm was used as the common comparator. Baseline patient population characteristics were compared along with treatment emergent adverse events. The relative overall response was compared using the Bucher method for indirect treatment comparison. Upper and lower limits of the 95% confidence intervals were also calculated. Results: A hazard ratio of 1.03 was obtained using indirect treatment comparison, indicating that these agents have similar overall response rates. The upper and lower limits of the confidence intervals were 0.66 and 1.59 which makes the comparison statistically insignificant. Inclusion of baseline patient characteristics were also modeled and did not significantly alter the outcome. Simulation studies of patient compliance and disease progression due to discontinuation/suspension secondary to adverse drug related reactions tends to favor vimseltinib. Conclusions: Vimseltinib appears to be as effective as pexidartinib in producing similar response rates as documented by radiological response by RECIST criteria. However, given that vimseltinib appears to have a better toxicity profile than pexidartinib, it may offer a better treatment option to patients with TGCT as both agents have been shown to have similar response rates.