靶向药物艾伏尼布治疗胶质瘤疗效强劲

Approximately 100,000 people worldwide are diagnosed with diffuse glioma every year. glioma); accounts for less than 1% of all newly diagnosed cancers but has high morbidity and mortality. As malignant brain tumors, diffuse gliomas include low-grade glioma (LGG) and glioblastoma. About 70% of low-grade gliomas have isocitrate dehydrogenase 1 (IDH1) gene mutations. Ivosidenib is a first-in-class, selective, potent oral targeted inhibitor for cancers with IDH1 gene mutations. The drug is being tested in patients with solid tumors.

Investigators conducted a multicenter, open-label, phase I, dose-escalation and expansion study of ivosidenib in patients with mIDH1 solid tumors. Ivosidenib is administered orally daily in a 28-day cycle. The primary endpoint is the safety and tolerability of oral ivosidenib alone and determination of the maximum tolerated dose or phase II recommended dose of ivosidenib.

Secondary endpoints were dose-limiting toxicities in one-cycle dose escalation, pharmacokinetic and pharmacodynamic characteristics of ivonib, and preliminary clinical response (with RANO LGG standard assessment). The results showed that ivosidenib was well tolerated in 66 patients with advanced glioma, and no dose-limiting toxicities were reported. Maximum tolerated dose not reached; 500 once daily mg dose as an expansion cohort. The incidence of grade ≥3 adverse events was 19.7%; 3% (n = 2) of adverse events were treatment-related.

In patients with non-enhancing glioma (n = 35), the objective response rate was 2.9%, and 1 case achieved partial response. Thirty of 35 (85.7%) patients with non-enhancing glioma achieved stable disease, while 14 of 31 (45.2%) patients with enhancing glioma achieved stable disease. The median progression-free survival of ivosidenib in the non-enhancing glioma group was much higher than that in the enhancing glioma group, which was 13.6 months and 1.4 months respectively. An exploratory analysis showed that ivosidenib significantly reduced the size and growth rate of non-enhancing gliomas.

Therefore, in patients with mIDH1 advanced glioma, 500 once daily mg of ivosidenib not only extended the patient's disease control time and reduced the growth rate of non-enhancing glioma, but also had a good safety profile. Glioma is a highly malignant cancer in my country, with a relatively poor prognosis and limited treatment options. It is gratifying that in recent years, there have been more and more studies on targeted drugs, and we expect that new treatment models can further extend the survival period of patients and improve the quality of life.

Reference: Ivosidenib in Isocitrate Dehydrogenase 1 - Mutated Advanced Glioma