Phase II Trial of Nilotinib in PDGFR-alpha Enriched Recurrent High-Grade Gliomas
David Piccioni, Tiffany M Juarez, Sneha L Kesari, Lara Rose, Natsuko Nomura, Santosh KesariAbstract
Purpose
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. 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 clinical benefit in patients in earlier lines of treatment.