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 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 -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. NCT01140568, registered 08 June 2010.