Impact of Frontline Ivosidenib on Volumetric Growth Patterns in Isocitrate Dehydrogenase-mutant Astrocytic and Oligodendroglial Tumors

被引：6

作者：

Kamson, David Olayinka ^{[1
,2
]}

Puri, Sushant ^{[2
,3
]}

Sang, Yingying ^{[4
]}

Shi, Meihui Jessica ^{[1
]}

Blair, Lindsay ^{[2
]}

Blakeley, Jaishri O. ^{[1
,2
]}

Laterra, John ^{[1
,2
]}

机构：

[1] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Sch Med, Dept Oncol, Baltimore, MD USA

[2] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD USA

[3] NCI, Neurooncol Branch, NIH, Bethesda, MD USA

[4] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA

来源：

CLINICAL CANCER RESEARCH | 2023年 / 29卷 / 23期

关键词：

MENINGIOMA CLINICAL-TRIALS; DRUG ACTIVITY; CHEMOTHERAPY; IDH1;

D O I：

10.1158/1078-0432.CCR-23-0585

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

<bold>Purpose: </bold>Isocitrate dehydrogenase (IDH)-mutant gliomas are usually treated with radiotherapy and chemotherapy, which increases the risk for neurocognitive sequelae during patients' most productive years. We report our experience using off-label first-in-class mutant IDH1 inhibitor ivosidenib and its impact on tumor volume in IDH-mutant gliomas. <bold>Experimental design: </bold>We retrospectively analyzed patients ages >= 18 years with radiation/chemotherapy-na & iuml;ve, mutant IDH1, nonenhancing, radiographically active, grade 2/3 gliomas, and >= 2 pretreatment and >= 2 on-treatment ivosidenib MRIs. T2/FLAIR-based tumor volumes, growth rates, and progression-free survival (PFS) were analyzed. log-linear mixed-effect modeling of growth curves adjusted for grade, histology, and age was performed. <bold>Results: </bold>We analyzed 116 MRIs of 12 patients [10 males, median age 46 years (range: 26-60)]: 8 astrocytomas (50% grade 3) and 4 grade 2 oligodendrogliomas. Median on-drug follow-up was 13.2 months [interquartile range (IQR): 9.7-22.2]. Tolerability was 100%. A total of 50% of patients experienced >= 20% tumor volume reduction on-treatment and absolute growth rate was lower during treatment (-1.2 +/- 10.6 cc/year) than before treatment (8.0 +/- 7.7 cc/year; P <= 0.05). log-linear models in the Stable group (n = 9) showed significant growth before treatment (53%/year; P = 0.013), and volume reduction (-34%/year; P = 0.037) after 5 months on treatment. After treatment, volume curves were significantly lower than before treatment (after/before treatment ratio 0.5; P < 0.01). Median time-to-best response was 11.2 (IQR: 1.7-33.4) months, and 16.8 (IQR: 2.6-33.5) months in patients on drug for >= 1 year. PFS at 9 months was 75%. <bold>Conclusions: </bold>Ivosidenib was well tolerated and induced a high volumetric response rate. Responders had significant reduction in tumor growth rates and volume reductions observed after a 5-month delay. Thus, ivosidenib appears useful to control tumor growth and delay more toxic therapies in IDH-mutant nonenhancing indolently growing gliomas.

引用

页码：4863 / 4869

页数：7