Fosaprepitant versus aprepitant in the prevention of chemotherapy-induced nausea and vomiting in patients receiving cisplatin-based chemotherapy: a multicenter, randomized, double-blind, double-simulated, positive-controlled phase III trial

Zhonghan Zhang; Yunpeng Yang; Ping Lu; Xiaoqin Li; Jianhua Chang; Rongsheng Zheng; Lei Zhou; Shaoshui Chen; Xiaopin Chen; Biyong Ren; Wei Gu; Xiaodong Jiang; Jiyong Peng; Miaolong Huang; Guosheng Feng; Peng Shen; Qingyuan Zhang; Baihong Zhang; Yan Huang; Jingdong He; Yinglan Chen; Jingxu Cao; Hong Wang; Wei Li; Huiping Wan; Kejun Nan; Zijun Liao; Cuiying Zhang; Zhong Lin; Diansheng Zhong; Qing Xu; Hailong Liu; Tao Sun; Yanming Deng; Li Zhang

doi:10.21037/atm.2019.12.158

Fosaprepitant versus aprepitant in the prevention of chemotherapy-induced nausea and vomiting in patients receiving cisplatin-based chemotherapy: a multicenter, randomized, double-blind, double-simulated, positive-controlled phase III trial

Ann Transl Med. 2020 Mar;8(5):234. doi: 10.21037/atm.2019.12.158.

Authors

Zhonghan Zhang¹, Yunpeng Yang¹, Ping Lu², Xiaoqin Li³, Jianhua Chang⁴, Rongsheng Zheng⁵, Lei Zhou⁶, Shaoshui Chen⁷, Xiaopin Chen⁸, Biyong Ren⁹, Wei Gu¹⁰, Xiaodong Jiang¹¹, Jiyong Peng¹², Miaolong Huang¹³, Guosheng Feng¹⁴, Peng Shen¹⁵, Qingyuan Zhang¹⁶, Baihong Zhang¹⁷, Yan Huang¹, Jingdong He¹⁸, Yinglan Chen¹⁹, Jingxu Cao²⁰, Hong Wang²¹, Wei Li²², Huiping Wan²³, Kejun Nan²⁴, Zijun Liao²⁵, Cuiying Zhang²⁶, Zhong Lin²⁷, Diansheng Zhong²⁸, Qing Xu²⁹, Hailong Liu³⁰, Tao Sun³¹, Yanming Deng³², Li Zhang¹

Affiliations

¹ Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.
² Oncology Internal Medicine, the First Affiliated Hospital of Xinxiang Medical College, Xinxiang 453000, China.
³ Oncology Department, Jiangsu University Affiliated Hospital, Zhenjiang 212031, China.
⁴ Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai 200000, China.
⁵ Oncology Internal Medicine, the First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, China.
⁶ Oncology Department, Beijing Century Temple Hospital, Beijing 100000, China.
⁷ Oncology Department, Binzhou Medical University Hospital, Binzhou 256602, China.
⁸ Department of Medical Oncology, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400000, China.
⁹ Department of Oncology, Chongqing Three Gorges Central Hospital, Chongqing 400000, China.
¹⁰ Department of Respiratory Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing 210029, China.
¹¹ Department of Oncology, the First People's Hospital of Lianyungang, Lianyungang 222002, China.
¹² Oncology Department, Jiangxi Pingxiang People's Hospital, Pingxiang 337055, China.
¹³ Department of Thoracic Surgery, People's Hospital of Northern Guangdong, Shaoguan 512000, China.
¹⁴ Department of Chemotherapy, the People's Hospital of Guangxi Zhuang Autonomous Region, Nanning 530000, China.
¹⁵ Chemotherapy Ward, the First Affiliated Hospital of Zhejiang University, Hangzhou 310000, China.
¹⁶ First Ward of Internal Medicine of Mammary Gland, Harbin Medical University Cancer Hospital, Harbin 150000, China.
¹⁷ Department of Oncology, the 940th Hospital of Joint Logistics Support Force of People's Liberation Army, Lanzhou 730030, China.
¹⁸ Department of Medical Oncology, Huai'an First People's Hospital, Huai'an 223001, China.
¹⁹ Thoracic Neoplasms, Jiangxi Provincial Cancer Hospital, Nanchang 330000, China.
²⁰ Oncology Department, Hospital of Armed Police Force, Beijing 100000, China.
²¹ Oncology Department, the Third Hospital of Nanchang City, Nanchang 330000, China.
²² Department of Medical Oncology, the First Bethune Hospital of Jilin University, Changchun 130000, China.
²³ Oncology Department, Jiangxi Provincial People's Hospital, Nanchang 330000, China.
²⁴ Department of Medical Oncology, Xi'an Jiaotong University the First Hospital, Xi'an 710000, China.
²⁵ Department of Medical Oncology, Shaanxi Provincial Tumor Hospital, Xi'an 710000, China.
²⁶ Oncology Internal Medicine, Inner Mongolia People's Hospital, Huhehaote 010000, China.
²⁷ Oncology Center, the Fifth Affiliated Hospital Sun Yat-sen University, Zhuhai 519000, China.
²⁸ The Medical Department, Tianjin Medical University General Hospital, Tianjin 300052, China.
²⁹ Department of Oncology, Shanghai Tenth People's Hospital of Tongji University, Shanghai 200000, China.
³⁰ Oncology, Chenzhou No. 1 People's Hospital, Chenzhou 423099, China.
³¹ Galactophore Clinic, Liaoning Cancer Hospital and Institute, Shenyang 110000, China.
³² Department of Cancer Center, Foshan First People's Hospital, Foshan 528000, China.

Abstract

Background: To establish the role of antiemetic therapy with neurokinin-1 (NK-1) receptor antagonists (RAs) in Chinese patients associated with cisplatin-base chemotherapy regimens, this study evaluated the efﬁcacy and safety of single-dose intravenous fosaprepitant-based triple antiemetic regimen to a 3-day orally aprepitant-based antiemetic triplet schedule for the prevention of chemotherapy-induced nausea and vomiting (CINV).

Methods: A randomized, double-blind, positive-control design was used to test the noninferiority of fosaprepitant towards aprepitant. Patients receiving cisplatin-base (≥50 mg/m²) chemotherapy were administrated palonosetron and dexamethasone with a single-dose fosaprepitant (150 mg on day 1) or a standard aprepitant regimen (125 mg on day 1, 80 mg on day 2 and day 3). The primary endpoint was complete response (CR) during overall phase (OP). Secondary endpoints include CR during acute phase (AP) and delayed phase (DP), no vomiting and no significant nausea during OP, AP and DP. Accrual of 324 patients per treatment arm was planned to conﬁrm noninferiority with expected CR of 75% and noninferiority margin of minus 10 percentage points.

Results: A total of 648 patients were randomly assigned, and 644 were evaluable for efﬁcacy and safety. Antiemetic efficacy of CR during the OP with fosaprepitant and aprepitant was equivalent (71.96% versus 69.35%, P=0.4894). And a between-group difference of 2.61 percentage points was finally achieved (95% CI, -4.42 to 9.64) within predeﬁned bounds for noninferiority (primary end point achieved). Both regimens were well tolerated and commonly reported adverse events (≥1%) were similar between these two group.

Conclusions: Single-dose intravenous fosaprepitant (150 mg) combined with palonosetron and dexamethasone was well tolerated and demonstrated noninferior control of CINV to aprepitant-based triple regimen in Chinese patients treating with cisplatin-base chemotherapy.

Keywords: Chemotherapy-induced nausea and vomiting (CINV); aprepitant; fosaprepitant; highly emetogenic chemotherapy; neurokinin-1 receptor antagonists.