Gastric cancer is the fifth most common cause of cancer and is the third most common cause of cancer-related mortality.1 First-line treatment of patients with locally advanced, unresectable, and/or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma generally consists of chemotherapy and/or chemoradiation, which may improve quality of life and extend survival time, but durable responses are disappointing and median survival time remains <2 years.1 Recently, immunotherapy has demonstrated promise in clinical studies in creating durable responses when used to treat gastric or GEJ cancer.1 The global phase 3 RAINBOW clinical trial demonstrated that in patients with advanced, fluoropyrimidine- and platinum-resistant gastric or GEJ adenocarcinoma, ramucirumab plus paclitaxel treatment improved overall survival compared with placebo plus paclitaxel.1
RAINBOW-Asia was a bridging phase 3 study performed at treatment centers in China, the Philippines, Malaysia, and Thailand to investigate the efficacy and safety of ramucirumab plus paclitaxel in 440 adult Asian patients with locally advanced or metastatic, unresectable gastric or GEJ adenocarcinoma. Eligible patients were previously treated with fluoropyrimidine and platinum-based chemotherapy. They were randomized 2:1 into 2 treatment arms, and further randomization was performed based on Eastern Cooperative Oncology Group performance status and if peritoneal metastasis were present. Arm 1 patients received 8 mg/kg ramucirumab intravenously on days 1 and 15 plus 80 mg/m2 paclitaxel intravenously on days 1, 8, and 15 of the 28-day treatment cycle. Arm 2 patients received 8 mg/kg placebo intravenously on days 1 and 15 plus 80 mg/m2 paclitaxel intravenously on days 1, 8, and 15 during the 28-day treatment cycle. The study’s primary end points were progression-free survival (PFS) and overall survival (OS).
Median PFS was 4.14 months in arm 1 patients and 3.15 months in arm 2 patients (hazard ratio [HR], 0.765; 95% confidence interval [CI], 0.613-0.955; P = .0184). Median OS in arm 1 was 8.71 months and 7.92 months in arm 2 (HR, 0.963; 95% CI, 0.771-1.203; P = .7426). Safety evaluation was performed using data from patients who had received ≥1 doses of the study treatment. Treatment-related adverse events grade ≥3 included decreased neutrophil count in 54% of arm 1 patients and 39% of arm 2 patients, anemia in 16% of arm 1 patients and 17% of arm 2 patients, decreased white blood cell count in 43% of arm 1 patients and 29% of arm 2 patients, febrile neutropenia in 6% of arm 1 patients and <1% of arm 2 patients, and hypertension in 7% of arm 1 patients and 6% of arm 2 patients.
Ramucirumab plus paclitaxel demonstrated a PFS and OS advantage over placebo plus paclitaxel in Asian patients with advanced gastric and GEJ cancer previously treated with chemotherapy.
Xu RH, Zhang Y, Pan H, et al. 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. Lancet Gastroenterol Hepatol. 2021;6:1015-1024.
- Cascinu S, Bodoky G, Muro K, et al. Tumor response and symptom palliation from RAINBOW, a phase III trial of ramucirumab plus paclitaxel in previously treated advanced gastric cancer. Oncologist. 2021;26:e414-e424.