Phase II trial of nilotinib in PDGFR-alpha-enriched recurrent high-grade gliomas

Background. This phase II clinical trial evaluated the safety and efficacy of nilotinib in patients with recurrent, platelet-derived growth factor receptor alpha (PDGFRA)-enriched high-grade gliomas. Methods. Thirty-four adult patients with PDGFRA-enriched recurrent high-grade gliomas were enrolled. Study treatment consisted of nilotinib 400 mg administered twice daily in 28-day cycles. Safety and clinical activity were evaluated. Results. Median lines of prior therapy were 2 (range 1–7) and 9 of 34 (26%) patients received prior bevacizumab. Four patients had PDGFRA gene amplification, and 30 had PDGFRA overexpression by immunohistochemistry. Overall, nilotinib was well tolerated.The most common treatment-related toxicities were increased ALT, joint pain, and hyponatremia. No treatment-related grade 4 or 5 adverse events occurred.The best response was stable disease (SD) for 8 patients and complete response (CR) for one patient with glioblastoma.The median PFS was 1.45 months (95% CI 0.986–2.07) and the median OS was 6.6 months (95% CI 4.9–18.3).The patient with a CR was an MGMT-unmethylated GBM with PDGFRA overexpression by IHC, and maintained a durable response for over 5 years. Conclusion. Nilotinib was well tolerated with limited benefit in this enriched population of patients. Further studies are warranted to determine the clinical benefit in patients in earlier lines of treatment.