Adjuvant Temozolomide Chemotherapy With or Without Interferon Alfa Among Patients With Newly Diagnosed High-grade Gliomas: A Randomized Clinical Trial.

作者信息

Guo Chengcheng, Yang Qunying, Xu Pengfei, Deng Meiling, Jiang Taipeng, Cai Linbo, Li Jibin, Sai Ke, Xi Shaoyan, Ouyang Hui, Liu Mingfa, Li Xianming, Li Zihuang, Ni Xiangrong, Cao Xi, Li Cong, Wu Shaoxiong, Du Xiaojing, Su Jun, Xue Xiaoying, Wang Yiming, Li Gang, Qin Zhiyong, Yang Hui, Zhou Tao, Liu Jinquan, Hu Xuefeng, Wang Jian, Jiang Xiaobing, Lin Fuhua, Zhang Xiangheng, Ke Chao, Lv Xiaofei, Lv Yanchun, Hu Wanming, Zeng Jing, Chen Zhenghe, Zhong Sheng, Wang Hairong, Chen Yinsheng, Zhang Ji, Li Depei, Mou Yonggao, Chen Zhongping

机构信息

Department of Neurosurgery and Neuro-oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China.

Department of Radiation, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China.

出版信息

JAMA Netw Open. 2023 Jan 3;6(1):e2253285. doi: 10.1001/jamanetworkopen.2022.53285.

DOI:10.1001/jamanetworkopen.2022.53285

PMID:36705923

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11839150/

Abstract

IMPORTANCE

High-grade gliomas (HGGs) constitute the most common and aggressive primary brain tumor, with 5-year survival rates of 30.9% for grade 3 gliomas and 6.6% for grade 4 gliomas. The add-on efficacy of interferon alfa is unclear for the treatment of HGG.

OBJECTIVES

To compare the therapeutic efficacy and toxic effects of the combination of temozolomide and interferon alfa and temozolomide alone in patients with newly diagnosed HGG.

DESIGN, SETTING, AND PARTICIPANTS: This multicenter, randomized, phase 3 clinical trial enrolled 199 patients with newly diagnosed HGG from May 1, 2012, to March 30, 2016, at 15 Chinese medical centers. Follow-up was completed July 31, 2021, and data were analyzed from September 13 to November 24, 2021. Eligible patients were aged 18 to 75 years with newly diagnosed and histologically confirmed HGG and had received no prior chemotherapy, radiotherapy, or immunotherapy for their HGG.

INTERVENTIONS

All patients received standard radiotherapy concurrent with temozolomide. After a 4-week break, patients in the temozolomide with interferon alfa group received standard temozolomide combined with interferon alfa every 28 days. Patients in the temozolomide group received standard temozolomide.

MAIN OUTCOMES AND MEASURES

The primary end point was 2-year overall survival (OS). Secondary end points were 2-year progression-free survival (PFS) and treatment tolerability.

RESULTS

A total of 199 patients with HGG were enrolled, with a median follow-up time of 66.0 (95% CI, 59.1-72.9) months. Seventy-nine patients (39.7%) were women and 120 (60.3%) were men, with ages ranging from 18 to 75 years and a median age of 46.9 (95% CI, 45.3-48.7) years. The median OS of patients in the temozolomide plus interferon alfa group (26.7 [95% CI, 21.6-31.7] months) was significantly longer than that in the standard group (18.8 [95% CI, 16.9-20.7] months; hazard ratio [HR], 0.64 [95% CI, 0.47-0.88]; P = .005). Temozolomide plus interferon alfa also significantly improved median OS in patients with O6-methylguanine-DNA methyltransferase (MGMT) unmethylation (24.7 [95% CI, 20.5-28.8] months) compared with temozolomide (17.4 [95% CI, 14.1-20.7] months; HR, 0.57 [95% CI, 0.37-0.87]; P = .008). Seizure and influenzalike symptoms were more common in the temozolomide plus interferon alfa group, with 2 of 100 (2.0%) and 5 of 100 (5.0%) patients with grades 1 and 2 toxic effects, respectively (P = .02). Finally, results suggested that methylation level at the IFNAR1/2 promoter was a marker of sensitivity to temozolomide plus interferon alfa.

CONCLUSIONS AND RELEVANCE

Compared with the standard regimen, temozolomide plus interferon alfa treatment could prolong the survival time of patients with HGG, especially the MGMT promoter unmethylation variant, and the toxic effects remained tolerable.