Tap WD, et al. - Through two-phase 3 randomized trials with 120 patients with tenosynovial giant cell tumor (TGCT, a rare, locally aggressive neoplasm), the researchers assessed the safety and efficacy of pexidartinib (a colony-stimulating factor 1 receptor inhibitor) for cases that are not eligible for surgical resection. The most frequent pexidartinib-associated adverse events were alteration in hair color, fatigue, elevated aspartate aminotransferase, nausea, increase in alanine aminotransferase, and dysgeusia. Robust tumor response in TGCT with improvement in patient symptoms and functional outcomes was seen with pexidartinib, but with a risk of mixed or cholestatic hepatotoxicity. As the first systemic therapy with a strong response, in cases not amenable to improvement with surgery pexidartinib could be acknowledged as a possible treatment for TGCT associated with severe morbidity or functional limitations. The percentage of patients who achieved overall response was greater for pexidartinib vs placebo at week 25.