Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial

Wilke, H.; Muro, Kei; Cutsem, Éric Van; Oh, Sang Cheul; Bodoky, G.; Shimada, Yasuhiro; Hironaka, Shuichi; Sugimoto, Naotoshi; Lipatov, Oleg; Kim, Tae You; Cunningham, David; Rougier, Philippe; Komatsu, Yoshito; Ajani, Jaffer A.; Emig, Michael; Carlesi, Roberto; Ferry, David; Chandrawansa, Kumari; Schwartz, Jonathan D.; Ohtsu, Atsushi

doi:10.1016/s1470-2045(14)70420-6

Cited by 2,071 publications

(1,836 citation statements)

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“…PTX was comparable between the Japanese and Western populations and consistent with the safety profile seen in the RAINBOW overall results [6]. Neutropenia was one of the most frequently reported adverse events in both treatment arms, and the incidence in the PL ?…”

Section: Discussionsupporting

confidence: 78%

“…PTX versus PL ? PTX in OS (HR, 0.807), PFS (HR, 0.635), and ORR (28 % vs 16 %) [6]. In the present subpopulation analysis, benefits in PFS and ORR were observed in the RAM ?…”

Section: Discussionmentioning

confidence: 46%

“…The study design and procedures for RAINBOW have been previously published [6]. Eligible patients had metastatic or unresectable, locally advanced gastric or gastroesophageal junction adenocarcinoma and documented objective radiological or clinical disease progression during or within 4 months of the last dose of first-line platinum-based and fluoropyrimidine-based doublet therapy with or without anthracycline, and an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.…”

Section: Study Design and Patientsmentioning

confidence: 99%

“…Patients were randomly assigned, in a 1:1 ratio, to receive either ramucirumab at 8 mg/kg or placebo intravenously on days 1 and 15 plus paclitaxel at 80 mg/m 2 intravenously on days 1, 8, and 15 of a 28-day cycle [6]. Randomization was stratified by three factors: geographic region (region 1, Australia, Europe, Israel, and USA; region 2, Argentina, Brazil, Chile, and Mexico; region 3, Hong Kong, Japan, Singapore, South Korea, and Taiwan); time to progression (TTP) from the start of first-line chemotherapy (less than 6 months vs 6 months or more); and disease measurability (measurable vs nonmeasurable disease).…”

Section: Treatmentmentioning

confidence: 99%

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Subgroup analyses of the safety and efficacy of ramucirumab in Japanese and Western patients in RAINBOW: a randomized clinical trial in second-line treatment of gastric cancer

et al. 2015

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Background We evaluated the safety and efficacy of ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients previously treated for advanced gastric or gastroesophageal junction adenocarcinoma in Japanese and Western subgroups from the RAINBOW trial. Methods Patients received ramucirumab at 8 mg/kg or placebo (days 1 and 15) plus paclitaxel at 80 mg/m 2 (days 1, 8, and 15 of a 28-day cycle). End points were compared between treatment arms within Japanese (N = 140) and Western (N = 398) populations. Results The incidence of adverse events of grade 3 or higher was higher for ramucirumab plus paclitaxel in both populations (Japanese population, 83.8 % vs 52.1 %; Western population, 79.1 % vs 61.9 %). Neutropenia was the commonest adverse event of grade 3 or higher, with a higher incidence for ramucirumab plus paclitaxel (Japanese population, 66.2 % vs 25.4 %; Western population, 32.1 % vs 14.7 %). The incidence of febrile neutropenia was low and was similar between treatment arms in both populations. The overall survival hazard ratio was 0.88 (95 % Conclusions Safety profiles of the ramucirumab plus paclitaxel arm were similar between populations, though there was a higher incidence of neutropenia in Japanese patients. Progression-free survival and objective response rate improvements were observed for ramucirumab plus paclitaxel in both populations. ClinicalTrials.gov identifier: NCT01170663This

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Section: Discussionsupporting

confidence: 78%

“…PTX versus PL ? PTX in OS (HR, 0.807), PFS (HR, 0.635), and ORR (28 % vs 16 %) [6]. In the present subpopulation analysis, benefits in PFS and ORR were observed in the RAM ?…”

Section: Discussionmentioning

confidence: 46%

Section: Study Design and Patientsmentioning

confidence: 99%

Section: Treatmentmentioning

confidence: 99%

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Subgroup analyses of the safety and efficacy of ramucirumab in Japanese and Western patients in RAINBOW: a randomized clinical trial in second-line treatment of gastric cancer

et al. 2015

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“…In addition, the TBP strategy involves the additional cost of trastuzumab, and the current standard care in second-line treatment for gastric cancer is paclitaxel plus ramucirumab regardless of HER2 status (27); consequently, a certain degree of prudence is required when adapting this Table II. Adverse events of all grades and grades 3-4 occurring in the non-TBP and TBP groups.…”

Section: Discussionmentioning

confidence: 99%

Correlation between human epidermal growth factor receptor 2 expression level and efficacy of trastuzumab beyond progression in metastatic gastric cancer

Kadowaki¹,

Masuishi²,

Taniguchi³

et al. 2017

Oncology Letters

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Abstract. There is currently no clinical data regarding the efficacy of trastuzumab treatment for the progression of human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer (AGC) occurring during trastuzumab-based chemotherapy. The aim of this study was to retrospectively examine the clinical benefits of trastuzumab for HER2-positive AGC patients who progressed during first-line trastuzumab-based chemotherapy. Among the 108 patients treated with trastuzumab combined with fluoropyrimidine and cisplatin as first-line therapy, 46 HER2-positive AGC patients who received cytotoxic agents with or without trastuzumab subsequent to disease progression were included. Of these, the efficacy and safety outcomes of 26 patients who continued trastuzumab were compared with those of the 20 patients who discontinued trastuzumab. No difference in response rate (18.2 vs. 15.8%, P=1.00) was observed between the two groups. Progression-free survival (PFS) time was numerically longer in the chemotherapy combination with trastuzumab group than in the chemotherapy combination without trastuzumab group (median, 4.0 vs. 2.3 months), with no significance [hazard ratio (HR), 0.63; P=0.14]. In the subset analysis, continuation of trastuzumab significantly improved PFS time in selected subgroups of patients with tumors exhibiting HER2 expression scores of 3+ (HR, 0.41; P=0.04), intestinal-type histology (HR, 0.32; P<0.01), and a first PFS time of >6 months (HR, 0.44; P=0.04). The survival times for the trastuzumab beyond progression (TBP) and non-TBP groups were similar (HR, 1.06; P=0.88), with equivalent overall survival times in the subgroups with immunohistochemistry scores of 3+ (HR, 0.97; P=0.94), 0.53; P= 0.19), and a first PFS time of >6 months (HR, 0.62; P=0.31). There were no differences in the incidence rates of toxicity, including cardiac dysfunction, between the two groups. The study results suggest that selected HER2-positive AGC patients may benefit from trastuzumab continuation during first progression, and further prospective studies are warranted.

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Effect of First-line S-1 Plus Oxaliplatin With or Without Ramucirumab Followed by Paclitaxel Plus Ramucirumab on Advanced Gastric Cancer in East Asia

et al. 2019

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IMPORTANCE Ramucirumab, a human IgG 1 antibody against vascular endothelial growth factor receptor 2, has been shown to improve progression-free survival and overall survival in patients with advanced gastric cancer in the second-line setting. OBJECTIVE To compare progression-free survival for S-1 and oxaliplatin plus ramucirumab with that for S-1 and oxaliplatin plus placebo in patients with advanced gastric cancer. DESIGN, SETTING, AND PARTICIPANTS This phase 2, double-blind randomized clinical trial (RAINSTORM [First-line S-1 Plus Oxaliplatin With or Without Ramucirumab Followed by Paclitaxel Plus Ramucirumab in Patients With Advanced Gastric Cancer]) was conducted from October 12, 2015, to April 11, 2018, at 36 sites in Japan, South Korea, and Taiwan. Participants were chemotherapynaive patients (n = 189) with metastatic gastric or gastroesophageal adenocarcinoma. Analyses of the full analysis set and safety population were conducted between November 27, 2017, and June 4, 2018. INTERVENTIONS Patients randomized to the ramucirumab plus S-1 and oxaliplatin arm received S-1, 80 to 120 mg/d twice daily, on days 1 to 14 and oxaliplatin, 100 mg/m 2 , on day 1 with ramucirumab, 8 mg/kg, on days 1 and 8 in part A (21-day cycle). Patients randomized to the placebo plus S-1 and oxaliplatin arm received the same S-1 and oxaliplatin dosage as well as placebo on days 1 and 8 in part A. Eligible patients received second-line paclitaxel, 80 mg/m 2 , on days 1, 8, and 15 and ramucirumab, 8 mg/kg, on days 1 and 15 in part B (28-day cycle). MAIN OUTCOMES AND MEASURES The primary end point was progression-free survival, analyzed using the stratified log-rank test; the hazard ratio (HR) was estimated using the stratified Cox proportional hazards regression model. Secondary end points included overall survival and adverse events. RESULTS In total, 189 patients were randomized and received treatment: 96 to the ramucirumab plus S-1 and oxaliplatin arm and 93 to the placebo plus S-1 and oxaliplatin arm. Among the 189 patients, 121 (64.0%) were male, and the median (range) age was 62.0 (26-84) years. Median progression-free survival was not prolonged in the ramucirumab plus S-1 and oxaliplatin arm

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Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial

Cited by 2,071 publications

References 28 publications

Subgroup analyses of the safety and efficacy of ramucirumab in Japanese and Western patients in RAINBOW: a randomized clinical trial in second-line treatment of gastric cancer

Subgroup analyses of the safety and efficacy of ramucirumab in Japanese and Western patients in RAINBOW: a randomized clinical trial in second-line treatment of gastric cancer

Correlation between human epidermal growth factor receptor 2 expression level and efficacy of trastuzumab beyond progression in metastatic gastric cancer

Effect of First-line S-1 Plus Oxaliplatin With or Without Ramucirumab Followed by Paclitaxel Plus Ramucirumab on Advanced Gastric Cancer in East Asia

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