Induction chemotherapy plus radiotherapy alone versus cisplatin-based concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma: An open-label, non-inferiority, randomized phase 3 trial.

person MingYuan Chen Sun Yat-sen University Cancer Center, Guangzhou, China info_outline MingYuan Chen, Peiyu Huang, Xuyin Chen, Xi Ding, Guo Ling, Hao-Yuan Mo, Chongyang Duan, Li Ling, Xiong Zou, You-Ping Liu, Rui You, Yulong Xie, Jingyu Cao, Sihan Liu, Zimeng Wang, Qi Yang, Fang Qiu, Yijun Hua, Kajia Cao, Dong-Hua Luo

Authors person MingYuan Chen Sun Yat-sen University Cancer Center, Guangzhou, China info_outline MingYuan Chen, Peiyu Huang, Xuyin Chen, Xi Ding, Guo Ling, Hao-Yuan Mo, Chongyang Duan, Li Ling, Xiong Zou, You-Ping Liu, Rui You, Yulong Xie, Jingyu Cao, Sihan Liu, Zimeng Wang, Qi Yang, Fang Qiu, Yijun Hua, Kajia Cao, Dong-Hua Luo Organizations Sun Yat-sen University Cancer Center, Guangzhou, China, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China, Sun yat-sen University Cancer Center, Guangzhou, China, Sun Yat-Sen University Cancer Center, Guangzhou, China, Nanfang Hospital, Southern Medical University, Guangzhou, China, Clinical Research Design Division, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China, Sun Yat-sen University Cancer Center (China), Guangzhou, China, Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Centre, State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, China Abstract Disclosures Research Funding Other Foundation the Key-Area Research and Development of Guangdong Province (2020B1111190001), the National Natural Science Foundation of China (No. 82002857, 82230034, 81874134), Sun Yat-Sen University Clinical Research 5010 Program (No. 2015010，2018015) Background: Cisplatin-based concurrent chemoradiotherapy (CCRT) has long been regarded as standard treatment for locoregionally advanced nasopharyngeal carcinoma (LA-NPC) due to its favorable local control. However, concurrent platinum is associated with intolerable toxicities and ineffective in preventing distant metastasis. Since IMRT enhances the local control and induction chemotherapy (IC) decreases the risk of distant failure, it is worth exploring whether IC plus IMRT alone regimen could replace CCRT for patients with LA-NPC. Methods: This open-label, phase 3, non-inferiority clinical trial was conducted from June 12, 2015 to April 30, 2019. Patients with stage T1-4N2-3 or T3-4N0-1 M0 NPC were randomly assigned (1:1) to receive gemcitabine (1000 mg/m²) and cisplatin (80 mg/m²) IC for 2 cycles followed by IMRT alone or IMRT plus concomitant weekly cisplatin (40 mg/m²) up to 7 cycles. 2-year failure-free survival was set as primary endpoint and non-inferiority margin of 10% was established. Efficacy analysis and safety analysis were dividedly performed in the intention-to-treat and safety population. Results: A total of 249 patients were enrolled, including 124 patients in IC group and 125 patients in CCRT group. Median follow-up time was 60 months (IQR, 48-71). 2-year failure-free survival was 90.2% in IC group versus 86.3% in CCRT group, with an HR of 0.818 (95% CI, 0.479-1.397) and absolute difference of 3.9% (1-sided 95%CI, -4.2 to 11.9). No significant differences were observed between groups in overall survival, locoregional relapse, or distant metastasis. Compared with CCRT group, fewer grade ≥3 AEs occurred in IC group (47.5% vs 61.5%, p = 0.015), including leucopenia, anemia, mucositis, nausea and dysphagia. The IC group had significantly better QoL during and short periods after IMRT, including domains of global health status, physical functioning, fatigue, nausea and vomiting, pain, and appetite loss. Conclusions: For LA-NPC, gemcitabine and cisplatin induction chemotherapy plus IMRT alone was not inferior in 2-year failure-free survival to concurrent chemoradiotherapy. Clinical trial information: NCT02460887.