Nab-paclitaxel, cisplatin, and capecitabine versus cisplatin and gemcitabine as first line chemotherapy in patients with recurrent or metastatic nasopharyngeal carcinoma: randomised phase 3 clinical trial
Guoying Liu, Yan-Fang Ye, Yao-Fei Jiang, Jinna Chen, Wei‐Xiong Xia, Yisheng Huang, Tian-Sheng Gao, Yimin Liu, Ya-Ting Hou, Jianfei Li, Jiahao Liu, Nian Lu, Changlong Chen, Liang-Ru Ke, Hu Liang, Wei-Xin Bei, Wang‐Zhong Li, Shu-Hui Dong, Qin Liu, Changqing Xie, Herui Yao, Yan‐Qun Xiang
Abstract
Abstract Objective To compare the effectiveness and safety of nab-paclitaxel, cisplatin, and capecitabine (nab-TPC) with gemcitabine and cisplatin as an alternative first line treatment option for recurrent or metastatic nasopharyngeal carcinoma. Design Phase 3, open label, multicentre, randomised trial. Setting Four hospitals located in China between September 2019 and August 2022. Participants Adults (≥18 years) with recurrent or metastatic nasopharyngeal carcinoma. Interventions Patients were randomised in a 1:1 ratio to treatment with either nab-paclitaxel (200 g/m 2 on day 1), cisplatin (60 mg/m 2 on day 1), and capecitabine (1000 mg/m 2 twice on days 1-14) or gemcitabine (1 g/m 2 on days 1 and 8) and cisplatin (80 mg/m 2 on day 1). Main outcome measures Progression-free survival was evaluated by the independent review committee as the primary endpoint in the intention-to-treat population. Results The median follow-up was 15.8 months in the prespecified interim analysis (31 October 2022). As assessed by the independent review committee, the median progression-free survival was 11.3 (95% confidence interval 9.7 to 12.9) months in the nab-TPC cohort compared with 7.7 (6.5 to 9.0) months in the gemcitabine and cisplatin cohort. The hazard ratio was 0.43 (95% confidence interval 0.25 to 0.73; P=0.002). The objective response rate in the nab-TPC cohort was 83% (34/41) versus 63% (25/40) in the gemcitabine and cisplatin cohort (P=0.05), and the duration of response was 10.8 months in the nab-TPC cohort compared with 6.9 months in the gemcitabine and cisplatin cohort (P=0.009). Treatment related grade 3 or 4 adverse events, including leukopenia (4/41 (10%) v 13/40 (33%); P=0.02), neutropenia (6/41 (15%) v 16/40 (40%); P=0.01), and anaemia (1/41 (2%) v 8/40 (20%); P=0.01), were higher in the gemcitabine and cisplatin cohort than in the nab-TPC cohort. No deaths related to treatment occurred in either treatment group. Survival and long term toxicity are still being evaluated with longer follow-up. Conclusion The nab-TPC regimen showed a superior antitumoural efficacy and favourable safety profile compared with gemcitabine and cisplatin for recurrent or metastatic nasopharyngeal carcinoma. Nab-TPC should be considered the standard first line treatment for recurrent or metastatic nasopharyngeal carcinoma. Longer follow-up is needed to confirm the benefits for overall survival. Trial registration Chinese Clinical Trial Registry ChiCTR1900027112.