Toxicity Data From the CRUX Trial of Ruxolitinib in High-Grade Gliomas

Manmeet Ahluwalia, MD, the chief of Medical Oncology, chief scientific officer & deputy director at Miami Cancer Institute of Baptist Health South Florida, discusses results from the CRUX trial (NCT03514069) which were presented during the 2023 American Society of Clinical Oncology Annual Meeting.

According to findings from the study, ruxolitinib (Jakafi) with 75 mg/m² of temozolomide with radiation of 60 Gy over 6 weeks is safe, feasible, and demonstrated positive efficacy among patients with WHO Grade 3-4 newly-diagnosed high-grade gliomas.

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0:08 | At ASCO 2023, we were very excited to present a final report of CRUX study, which was looking at the JAK/STAT inhibitor ruxolitinib in patients with newly diagnosed high-grade gliomas. The outcomes for patients with high-grade gliomas is fairly dismal, despite the advances in surgery, radiation, and chemotherapy. Hence, novel agents like ruxolitinib are urgently needed. Ruxolitinib targets the JAK/STAT pathway that has been associated with tumor progression and worse outcomes in patients with glioblastoma. Hence, we combined this agent with radiation alone in the MGMT unmethylated patients, and we combined it along with temozolomide and radiation in the MGMT methylated patients because temozolomide only confers a 21 day benefit in patients with unmethylated MGMT glioblastoma.

1:06 | What we found out was that the agent ruxolitinib was extremely well-tolerated, both in combination with either radiation or with temozolomide and radiation. The highest dose of ruxolitinib that was given on this trial without any dose-limiting toxicity was 20 milligrams BID dosing. We also found that the outcomes of the patients treated with ruxolitinib along with radiation in arm 1 unmethylated patients and ruxolitinib and temozolomide with radiation appear promising compared with the historical controls with these patients. Hence, currently, we are planning a phase 2 trial looking at ruxolitinib along with radiation and temozolomide in patients with glioblastoma.