SAN FRANCISCO – Patients with metastatic gastric or gastroesophageal junction adenocarcinoma benefit from treatment with ramucirumab regardless of their age, according to findings from an exploratory subgroup analysis of the phase III RAINBOW and REGARD studies.
The findings, which show at least a trend toward improvements in most age categories, are important given that nearly two-thirds of patients with these cancers are diagnosed at over age 65 years, and more than half of those are over age 75 years, Kei Muro, MD, reported at the symposium sponsored by ASCO, ASTRO, the American Gastroenterological Association, and the Society of Surgical Oncology.
“At the other end of the age spectrum, there is evidence that young age can also be an unfavorable prognostic characteristic for gastric cancer,” said Dr. Muro of Aichi Cancer Center Hospital in Nagoya, Japan.
Both RAINBOW and REGARD demonstrated statistically significant and clinically meaningful overall and progression-free survival benefits and acceptable and manageable toxicity with ramucirumab among patients with advanced gastric cancer who were randomized, in the second-line treatment setting, to receive active treatment with the fully humanized monoclonal antibody directed against vascular endothelial growth factor receptor–2 or placebo.
RAINBOW subjects were randomized 1:1 to receive 8 mg/kg of ramucirumab plus paclitaxel, or placebo plus paclitaxel. Among those aged 45 years or less (37 patients in each group), the median overall survival was 9.0 months for treatment vs. 4.2 months for placebo (hazard ratio, 0.555), and the median progression-free survival was 3.9 vs. 2.8 months (HR, 0.299).
The corresponding median overall survival rates for those aged 45-70 (225 and 230 patients in the groups, respectively), 70 or older (68 patients in each group), and 75 or older (20 and 16 patients in the groups, respectively) were 9.6 vs. 7.6 months (HR, 0.860), 10.8 vs. 8.6 months (HR, 0.881), and 11.0 vs. 11.0 months (HR, 0.971). The corresponding progression-free survival rates for those aged 45-70, 70 or older, and 75 or older were 4.6 vs. 2.8 months (HR, 0.649), 4.7 vs. 2.9 months (HR, 0.676), and 4.2 vs. 2.8 months (HR, 0.330).
REGARD subjects were randomized 2:1 to receive 8 mg/kg of ramucirumab plus best supportive care, or placebo plus best supportive care. Among those aged 45 years or less (37 patients in each group), the median overall survival was 9.0 vs. 4.2 months for treatment vs. placebo (HR, 0.555), and the median progression-free survival was 3.9 vs. 2.8 months (HR, 0.299).
Among REGARD subjects aged 45 years or less (28 and 12 patients in the groups, respectively), the median overall survival was 5.8 vs. 2.9 months for treatment vs. placebo (HR, 0.586), and the median progression-free survival was 1.9 vs. 1.4 months (HR, 0.270).
The corresponding median overall survival rates for those aged 45-70 (166 and 70 patients in the groups, respectively), 70 or older (44 and 35 patients in the groups, respectively), and 75 or older (21 and 13 patients in the groups, respectively) were 4.9 vs. 4.1 months (HR, 0.780), 5.9 vs. 3.8 months (HR, 0.730), and 9.3 vs. 5.1 months (HR, 0.588).
The corresponding progression-free survival rates for those aged 45-70, 70 or older, and 75 or older were 2.2 vs. 1.3 months (HR, 0.451), 2.1 vs. 1.4 months (HR, 0.559), 2.8 vs. 1.4 (HR, 0.420).
Baseline characteristics were generally well balanced between arms in each of the age subgroups, Dr. Muro said, noting that no obvious patterns for differential risks in terms of efficacy and adverse events of any grade or of grade 3 or greater were seen according to age. Discontinuation rates for adverse events were similar across different age groups, and quality of life, as determined by global health status, was satisfactory in all age groups.
“Despite some limitations regarding patient numbers in some age subgroups, this exploratory subgroup analysis supports the use of ramucirumab for the treatment of our patients with gastric cancer irrespective of age,” he concluded.
RAINBOW was funded by Eli Lilly. REGARD was funded by ImClone Systems. Dr. Muro reported receiving honoraria from Chugai Pharma, Merck Serono, Taiho Pharmaceutical, Takeda, Eli Lilly, and Yakult Honsha, as well as serving in a consulting or an advisory role for Ono, Merck Serono, and Eli Lilly, and receiving research funding from MSD, Daiichi Sankyo, Ono, Eisai, Pfizer, Chugai, Dainippon Sumitomo, Merck Serono, Janssen Pharmaceutical K.K., AstraZeneca, GlaxoSmithKline, and Kyowa Hakko Kirin.