In a Japanese phase III trial (RINDBeRG) reported in the Journal of Clinical Oncology, Sakai et al assessed whether the addition of ramucirumab to irinotecan would improve overall survival in third- or later-line treatment of patients with advanced or recurrent gastric or gastroesophageal cancer with progression on previous ramucirumab-based treatment.
As noted by the investigators, “Continuous use of antiangiogenic agents has demonstrated survival benefits in various cancers.”
Study Details
In the open-label multicenter trial, 402 patients were randomly assigned between February 2017 and August 2022 to receive continued ramucirumab at 8 mg/kg plus irinotecan at 150 mg/m2 every 2 weeks (n = 202) or irinotecan at the same dosage (n = 200). The primary endpoint of the study was overall survival.
Key Findings
Median overall survival was 9.4 months (95% confidence interval [CI] = 8.0–10.5 months) in the ramucirumab plus irinotecan group vs 8.5 months (95% CI = 8.0–9.3 months) in the irinotecan alone group (adjusted hazard ratio [HR] = 0.92, 95% CI = 0.74–1.13, P = .49). Rates at 6 and 12 months were 71.0% vs 69.8% and 36.5% vs 32.2%, respectively.
Median progression-free survival was 3.8 months (95% CI = 3.4–4.6 months) in the ramucirumab plus irinotecan group vs 2.8 months (95% CI = 2.2–3.5 months) in the irinotecan alone group (HR = 0.73, 95% CI = 0.59–0.89, P = .002). Rates at 6 months were 31.5% vs 17.6%.
Objective response rates were 22.1% vs 15.6% (P = .15). Disease control rates were 64.4% vs 52.1% (P = .03).
Adverse events of any grade with a higher incidence in the ramucirumab plus irinotecan group vs the irinotecan alone group included leukopenia (68.2% vs 48.0%), neutropenia (76.4% vs 59.7%), thrombocytopenia (32.8% vs 21.4%), hypoalbuminemia (50.8% vs 32.1%), oral mucositis (22.1% vs 8.2%), malaise (67.2% vs 54.1%), and diarrhea (58.5% vs 45.9%).
The investigators concluded: “Adding ramucirumab to irinotecan does not provide a significant advantage in [overall survival] over irinotecan alone in patients with [advanced or recurrent gastric or gastroesophageal cancer] who have progressed during ramucirumab-containing chemotherapy.”
Narikazu Boku, MD, PhD, of IMSUT Hospital, Institute of Medical Science, University of Tokyo, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the Research Support Program (National Cancer Center Research and Development Funds) and Eli Lilly. For full disclosures of all study authors, visit the Journal of Clinical Oncology.
