Efficacy and safety of weekly paclitaxel with or without ramucirumab as second-line therapy for the treatment of advanced gastric or gastroesophageal junction adenocarcinoma (RAINBOW-Asia): a randomised, multicentre, double-blind, phase 3 trial

Xu RH 1 , Zhang Y 2 , Pan H 3 , Feng J 4 , Zhang T 5 , Liu T 6 Show all authors , Qin Y 7 , Qin S 8 , Yin X 9 , Liu B 10 , Ba Y 11 , Yang N 9 , Voon PJ 12 , Tanasanvimon S 13 , Zhou C 14 , Zhang WL 14 , Shen L 15

Affiliations 

  • 1 Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China
  • 2 Department of Gastroenterology, Harbin Medical University Cancer Hospital, Harbin, China
  • 3 Department of Medical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China
  • 4 Department of Medical Oncology, Jiangsu Cancer Hospital, Nanjing, China
  • 5 Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
  • 6 Department of Medical Oncology, Fudan University Zhongshan Hospital, Shanghai Medical College, Shanghai, China
  • 7 Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
  • 8 Cancer Center of Nanjing Bayi Hospital, Nanjing Chinese Medicine University, Nanjing, China
  • 9 Gastroenterology and Urology Department, Hunan Cancer Hospital & The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China
  • 10 The Comprehensive Cancer Center of Drum Tower Hospital, Clinical Cancer Institute of Nanjing University, Nanjing, China
  • 11 Medical Oncology, Tianjin Cancer Hospital, Tianjin, China
  • 12 Radiotherapy and Oncology Department, Hospital Umum Sarawak, Kuching, Malaysia
  • 13 Division of Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
  • 14 Lilly China Drug Development and Medical Affairs Center, Eli Lilly and Company, Shanghai, China
  • 15 Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China. Electronic address: linshenpku@163.com
Lancet Gastroenterol Hepatol, 2021 12;6(12):1015-1024.
PMID: 34626550 DOI: 10.1016/S2468-1253(21)00313-7

Abstract

BACKGROUND: In the global phase 3 RAINBOW study, ramucirumab plus paclitaxel significantly improved overall survival compared with placebo plus paclitaxel in patients with advanced gastric or gastro-oesophageal junction (GEJ) adenocarcinoma. RAINBOW-Asia, a bridging study with similar design to RAINBOW, aimed to evaluate the efficacy and safety of ramucirumab plus paclitaxel for advanced gastric or GEJ adenocarcinoma in Asian, predominantly Chinese, patients.

METHODS: RAINBOW-Asia was a randomised, double-blind, placebo-controlled, phase 3 trial done at 32 centres in China, Malaysia, the Philippines, and Thailand. Adult patients (≥18 years) with metastatic or locally advanced, unresectable gastric or GEJ adenocarcinoma who previously received fluoropyrimidine-platinum-based chemotherapy were randomly assigned with a centralised interactive web response system in a 2:1 ratio to receive ramucirumab 8 mg/kg or placebo intravenously on days 1 and 15 plus paclitaxel 80 mg/m2 intravenously on days 1, 8, and 15 of every 28-day cycle. Randomisation was stratified by Eastern Cooperative Oncology Group performance status and presence of peritoneal metastases. The co-primary endpoints were progression-free survival and overall survival. Efficacy analyses were done in the intention-to-treat population, and safety analysis included patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, NCT02898077, and has been completed.

FINDINGS: Between March 2, 2017, and June 30, 2020, 440 patients were randomly assigned to receive ramucirumab plus paclitaxel (n=294) or placebo plus paclitaxel (n=146). Median progression-free survival was 4·14 months (95% CI 3·71-4·30) in the ramucirumab plus paclitaxel group compared with 3·15 months (2·83-4·14) in the placebo plus paclitaxel group (hazard ratio [HR] 0·765, 95% CI 0·613-0·955, p=0·0184). Median overall survival was 8·71 months (95% CI 7·98-9·49) in the ramucirumab plus paclitaxel group and 7·92 months (6·31-9·10) in the placebo plus paclitaxel group (HR 0·963, 95% CI 0·771-1·203, p=0·7426). The most common grade 3 or worse treatment-emergent adverse events were decreased neutrophil count (159 [54%] of 293 patients in the ramucirumab plus paclitaxel group vs 56 [39%] of 145 in the placebo plus paclitaxel group), decreased white blood cell count (127 [43%] vs 42 [29%]), anaemia (46 [16%] vs 24 [17%]), hypertension (21 [7%] vs nine [6%]), and febrile neutropenia (18 [6%] vs one [<1%]).

INTERPRETATION: These findings, along with the results from RAINBOW, support the use of ramucirumab plus paclitaxel as second-line therapy in a predominantly Chinese population with advanced gastric or GEJ adenocarcinoma.

FUNDING: Eli Lilly and Company, USA.

TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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