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Ramucirumab Demonstrates Survival Benefit in Gastric/GEJ Cancers, Regardless of Age

Published Online:3:04 PM, Mon January 23, 2017

Kei Muro, MD

In an analysis of 2 randomized trials,patients with advanced gastric or gastroesophageal juncture (GEJ) cancer derived a survival benefit from treatment with the monoclonal antibody ramucirumab, regardless of their age.

Patients younger than 45, 45 to 70, or older had statistically significant improvement with second-line ramucirumab alone or in combination with paclitaxel, as compared with best supportive care or compared with paclitaxel and placebo. Ramucirumab treatment was associated with hazard ratios for progression-free survival (PFS) of 0.52 and 0.64. Analysis of trial data by age group showed hazard reductions of 32% to 55%.

The survival analysis showed at least a trend toward improvement with ramucirumab, regardless of age group, consistent with the overall results of the 2 trials, which yielded hazard ratios of 0.64 and 0.81 in favor of the ramucirumab groups, as reported at the 2017 Gastrointestinal Cancers Symposium in San Francisco.

“These analyses suggest benefits of ramucirumab treatment in terms of progression-free survival and overall survival among young and elderly populations of patients in the REGARD and RAINBOW studies,” said Kei Muro, MD, a gastrointestinal oncologist at Aichi Cancer Center Hospital in Nagoya, Japan. “Toxicity profiles were comparable among age subgroups. Quality of life was satisfactory in all age groups in both trials.”

“Despite some limitations regarding patient numbers in some age subgroups,” he continued, “this exploratory analysis supports the use of ramucirumab for the treatment of gastric cancer, irrespective of age.”

Muro reported findings from a subgroup analysis of the REGARD and RAINBOW trials examining ramucirumab-based therapy in the second line for patients with advanced gastric/GEJ cancer. About 60% of patients with advanced gastric/GEJ cancer are 65 or older, and more than one-third of patients with the disease are aged 75 or older, providing the rationale for this subgroup analysis.

Investigators in REGARD enrolled and randomized 355 patients 2:1 to ramucirumab plus best supportive care (BSC) or to BSC and placebo. In the RAINBOW trial, 665 patients were randomized 1:1 to ramucirumab and paclitaxel or to placebo and paclitaxel. Both trials had overall survival as the primary endpoint.

The primary analysis of the REGARD trial showed a 22% reduction in the survival hazard for patients randomized to ramucirumab and a 52% reduction in the hazard for progression or death. Both differences achieved statistical significance versus the control group. The RAINBOW results demonstrated a 19% reduction in the survival hazard and a 36% reduction in the hazard for progression or death in favor of ramucirumab, both of which were statistically significant.

The subgroup analysis of REGARD showed hazard reductions of 41% for patients 45 or younger (n = 40), 22% for ages 45 to 70 (n = 236), and 27% for patients 70 or older (n = 79). All of the values were associated with overlapping confidence intervals. The PFS analysis yielded hazard reductions of 41%, 55%, and 44% among patients younger than 45, 45 to 70, or older. All of the values achieved statistical significance.

The age-based subgroup analysis of the RAINBOW trial yielded survival hazard ratios equivalent to reductions of 44% (n = 74), 14% (n = 455), and 12% (n = 136) across the youngest-to-oldest age groups, all favoring the ramucirumab arm. The hazard ratio for patients 45 or younger achieved statistical significance (95% CI, 0.33-0.93). The PFS subgroup analysis demonstrated hazard reductions of 50%, 35%, and 32% across the 3 age groups, and all were statistically significant.

Muro and colleagues also performed a subpopulation treatment effect pattern plot to assess efficacy and adverse effects across the 3 age subgroups. The analysis failed to reveal any obvious patterns of differential risk for efficacy or any adverse events (whether analyzed by any grade or grade ≥3) across the age groups.
Muro K, Cho J-Y, Bodoky G, et al. Efficacy and safety of ramucirumab (RAM) for metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma across age subgroups in two global phase 3 trials. J Clin Oncol. 2017;35 (suppl 4S; abstract 3).

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