Clinical trialPhase 3Stomach cancer

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

Lancet Oncol · 2014665 patients

Wilke H, Muro K, Van Cutsem E, Oh SC, Bodoky G, Shimada Y, et al. Lancet Oncol. 2014. 15:1224-1235

Study type: Clinical trial
Study name: RAINBOW
Phase: Phase 3
Design: Randomised, double-blind, placebo-controlled trial at 170 centres in 27 countries
Sample size: 665 patients
Source: Lancet Oncol · 2014
Trial registration: NCT01170663

In plain words

In patients whose advanced stomach cancer had grown after first chemotherapy, adding ramucirumab (a drug that blocks the tumour's blood vessel growth) to weekly paclitaxel raised the median survival from about 7.4 to 9.6 months. Low white blood cell counts and high blood pressure were more common with this combination.

Key results

9.6 vs 7.4 months

Median overall survival

HR 0.807 (95% CI 0.678–0.962); p=0.017

Drugs in this study:Paclitaxel (Taxol)

Dose and schedule cards

Ramucirumab + weekly paclitaxel (RAINBOW trial)

Advanced gastric or gastroesophageal junction adenocarcinoma progressing during or within 4 months after first-line chemotherapy (platinum + fluoropyrimidine)Cycle length: Every 28 daysOn the page “Stomach cancer” · After disease progression: second line and beyond

Advanced gastric or gastroesophageal junction adenocarcinoma progressing during or within 4 months after first-line chemotherapy (platinum + fluoropyrimidine)

Drug	Dose	Route	Schedule
Ramucirumab	8 mg/kg	IV (60 min; if tolerated, subsequent infusions over 30 min), before paclitaxel	Days 1 and 15
Paclitaxel	80 mg/m²	IV	Days 1, 8 and 15

Cycle length: Every 28 days
Duration: Until disease progression or unacceptable toxicity

Doses from the RAINBOW trial and the FDA label for ramucirumab. An intravenous H1 antihistamine (e.g., diphenhydramine) is required before each ramucirumab infusion; premedication for paclitaxel (corticosteroid, diphenhydramine and an H2 antagonist) as per the label. Monitor blood pressure and urine protein: for urine protein of 2 g or more per 24 hours, withhold ramucirumab until it falls below 2 g, then resume at 6 mg/kg; for more than 3 g per 24 hours or nephrotic syndrome, discontinue permanently. Discontinue permanently for severe bleeding, gastrointestinal perforation or an arterial thromboembolic event; withhold 28 days before elective surgery. In RAINBOW, grade ≥3 neutropenia occurred in 41% and hypertension in 14%.

On the page “Stomach cancer” · After disease progression: second line and beyond

Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.

Treatment arms and regimens

1Ramucirumab + paclitaxel

Ramucirumab 8 mg/kg IV (60-minute infusion; if tolerated, subsequent infusions over 30 minutes) on days 1 and 15, before paclitaxel 80 mg/m² IV on days 1, 8 and 15 of each 28-day cycle; until disease progression or unacceptable toxicity.

FDA label: an IV H1 antihistamine (such as diphenhydramine) before each ramucirumab infusion; for urine protein of 2 g or more per 24 hours, interrupt and resume at 6 mg/kg; for more than 3 g per 24 hours, discontinue permanently.

2Placebo + paclitaxel

Placebo IV on days 1 and 15, with paclitaxel 80 mg/m² IV on days 1, 8 and 15 of each 28-day cycle.

Source of the regimen details: Abstract of the paper (Lancet Oncol 2014) and the FDA label for Cyramza (section 2: infusion duration, premedication, dose modification for proteinuria)

Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.

Study population

Patients aged 18 or older with advanced gastric or gastro-oesophageal junction adenocarcinoma who had progressed during or within 4 months after first-line chemotherapy (platinum plus a fluoropyrimidine, with or without an anthracycline).

Endpoints

Primary endpoint: overall survival.

Safety and side effects

Grade 3 or higher adverse events (in more than 5% of patients in the ramucirumab group) versus placebo: neutropenia (41% versus 19%), leucopenia (17% versus 7%), hypertension (14% versus 2%), fatigue (12% versus 5%), anaemia (9% versus 10%) and abdominal pain (6% versus 3%); grade 3 or higher febrile neutropenia was low in both groups (3% versus 2%).

Per the FDA label for ramucirumab, blood pressure and urine protein must be monitored, and the drug is permanently discontinued for severe bleeding, gastrointestinal perforation or an arterial thromboembolic event.

Clinical significance and place in guidelines

RAINBOW made ramucirumab plus paclitaxel the standard second-line treatment for advanced gastric and gastro-oesophageal junction adenocarcinoma, and the ASCO 2026 guideline also lists it among the second-line options.

Limitations

Based on the abstract: the absolute survival benefit was about 2 months, and haematological toxicity and hypertension were more frequent with ramucirumab.

Original article (DOI)PubMed ClinicalTrials.gov

This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.