Cancer Res Treat.  2020 Apr;52(2):505-515. 10.4143/crt.2019.421.

Concurrent and Adjuvant Temozolomide for Newly Diagnosed Grade IIIGliomas without 1p/19q Co-deletion: A Randomized, Open-Label,Phase 2 Study (KNOG-1101 Study)

• Hwang K
• Kim TM
• Park CK
• Chang JH
• Jung TY
• Kim JH
• Nam DH
• Kim SH
• Yoo H
• Hong YK
• Kim EY
• Lee DE
• Joo J
• Kim YJ
• Choe G
• Choi BS
• Kang SG
• Kim JH
• Kim CY

• KMID: 2500335
• DOI: http://doi.org/10.4143/crt.2019.421

Abstract

Purpose
We investigated the efficacy of temozolomide during and after radiotherapy in Korean adults with anaplastic gliomas without 1p/19q co-deletion.
Materials and Methods
This was a randomized, open-label, phase 2 study and notably the first multicenter trial for Korean grade III glioma patients. Eligible patients were aged 18 years or older and had newly diagnosed non-co-deleted anaplastic glioma with an Eastern Cooperative Oncology Group performance status of 0-2. Patients were randomized 1:1 to receive radiotherapy alone (60 Gy in 30 fractions of 2 Gy) (control group, n=44) or to receive radiotherapy with concurrent temozolomide (75 mg/m2/day) followed by adjuvant temozolomide (150-200 mg/m2/day for 5 days during six 28-day cycles) (treatment group, n=40). The primary endpoint was 2-year progression-free survival (PFS). Seventy patients (83.3%) were available for the analysis of the isocitrate dehydrogenase 1 gene (IDH1) mutation status.
Results
The two-year PFS was 42.2% in the treatment group and 37.2% in the control group. Overall survival (OS) did not reach to significant difference between the groups. In multivariable analysis, age was a significant risk factor for PFS (hazard ratio [HR], 2.08; 95% confidence interval [CI], 1.04 to 4.16). The IDH1mutation was the only significant prognostic factor for PFS (HR, 0.28; 95% CI, 0.13 to 0.59) and OS (HR, 0.19; 95% CI, 0.07 to 0.50). Adverse events over grade 3 were seen in 16 patients (40.0%) in the treatment group and were reversible.
Conclusion
Concurrent and adjuvant temozolomide in Korean adults with newly diagnosed nonco- deleted anaplastic gliomas showed improved 2-year PFS. The survival benefit of this regimen needs further analysis with long-term follow-up at least more than 10 years.

Keyword

Anaplastic glioma; 1p/19q co-deletion; Temozolomide; Chemotherapy; Adjuvant treatment

Figure

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  Fig. 1. Kaplan-Meier curve of progression-free survival (A) and overall survival (B). CCRT, concurrent chemoradiotherapy; TMZ, temozolomide; RT, radiotherapy.

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  Fig. 2. Kaplan-Meier curve of progression-free survival (A, B) and overall survival (C, D) according to O6-methylguanineDNA methyltransferase (MGMT) promoter methylation status. CCRT, concurrent chemoradiotherapy; TMZ, temozolomide; RT, radiotherapy.

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  Fig. 3. Kaplan-Meier curve of progression-free survival (A, B) and overall survival (C, D) according to isocitrate dehydrogenase 1 (IDH1) mutation status. CCRT, concurrent chemoradiotherapy; TMZ, temozolomide; RT, radiotherapy

Reference

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