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
Mené sur 440 patients atteints d'un carcinome de l'estomac ou de la jonction oesogastrique de stade avancé, cet essai de phase III évalue l'efficacité, du point de vue de la survie sans progression et de la survie globale, de l'ajout du ramucirumab au paclitaxel en traitement de seconde ligne
Background : In the global phase 3 RAINBOW study, ramucirumab plus paclitaxel significantly improvedoverall survival compared with placebo plus paclitaxel in patients with advanced gastricor gastro-oesophageal junction (GEJ) adenocarcinoma. RAINBOW-Asia, a bridging studywith similar design to RAINBOW, aimed to evaluate the efficacy and safety of ramucirumabplus 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 doneat 32 centres in China, Malaysia, the Philippines, and Thailand. Adult patients (≥18years) with metastatic or locally advanced, unresectable gastric or GEJ adenocarcinomawho previously received fluoropyrimidine–platinum-based chemotherapy were randomlyassigned with a centralised interactive web response system in a 2:1 ratio to receiveramucirumab 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 stratifiedby Eastern Cooperative Oncology Group performance status and presence of peritonealmetastases. The co-primary endpoints were progression-free survival and overall survival.Efficacy analyses were done in the intention-to-treat population, and safety analysisincluded patients who received at least one dose of study treatment. This trial isregistered 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-freesurvival was 4·14 months (95% CI 3·71–4·30) in the ramucirumab plus paclitaxel groupcompared with 3·15 months (2·83–4·14) in the placebo plus paclitaxel group (hazardratio [HR] 0·765, 95% CI 0·613–0·955, p=0·0184). Median overall survival was 8·71months (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 decreasedneutrophil 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 cellcount (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 ramucirumabplus paclitaxel as second-line therapy in a predominantly Chinese population withadvanced gastric or GEJ adenocarcinoma.
The Lancet Gastroenterology & Hepatology , résumé, 2020