最新进展：Paxalisib一线治疗新诊断的胶质母细胞瘤显示出积极结果

Paxalisib is a small molecule inhibitor of the PI3K, AKT and mTOR pathways. In August 2020, the FDA granted paxalisib Fast Track designation for the treatment of newly diagnosed glioblastoma patients with unmethylated O6-methylguanine methyltransferase (MGMT) promoter status who have completed initial treatment with radiation and temozolomide.

The median overall survival (OS) in the intention-to-treat (ITT) population was 15.7 months, whereas historical data showed a median OS of 12.7 months in the same patient population treated with temozolomide. In the intention-to-treat population, median progression-free survival (PFS) was 8.4 months for patients treated with paxalisib and 5.3 months for patients treated with temozolomide (historical data).

Principal Investigator Patrick Y. Wen, Ph.D., Director of the Center for Neuro-Oncology at Dana-Farber Cancer Institute, said, "We are pleased to see the successful completion of the Phase 2 study of paxalisib. These data support the inclusion of paxalisib in the Phase 2/3 GBM AGILE study [NCT03970447] in glioblastoma, which has recently been expanded to Canada. Glioblastoma remains a disease in urgent need of new treatment options, and we look forward to learning from GBM Further data on paxalisib seen in AGILE study."

The study is divided into two phases, the first to determine appropriate dosing in newly diagnosed patients and the second to provide additional information on efficacy. Researchers also hope to determine overall survival (OS) and progression-free survival (PFS).

A total of 30 patients with recently diagnosed glioblastoma with unmethylated O6-methylguanine methyltransferase (MGMT) promoter status were included. In the first phase of the study, researchers determined that 60 mg of paxalisib once daily was the maximum tolerated dose.

The adjusted ITT group included 27 patients evaluable for efficacy. In this patient population, median OS increased to 15.9 months. The safety profile of paxalisib was clearly consistent with previously reported clinical trial data, with adverse effects including hyperglycemia, oral mucositis, and rash.

The glioblastoma AGILE pivotal study includes seven other trials using paxalisib. By the end of 2021, the researchers expect to have two more data. Final clinical data from this Phase 2 trial are expected to be released in the first quarter of 2022.

References:

https://www.cancernetwork.com/view/first-line-paxalisib-yields-positive-results-in-newly-diagnosed-glioblastoma