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

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In an analysis of 2 randomized trials,patients with advanced gastric or gastroesophageal juncture cancer derived a survival benefit from treatment with the monoclonal antibody ramucirumab, regardless of their age.<br /> &nbsp;

Kei Muro, MD

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.

&ldquo;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,&rdquo; said Kei Muro, MD, a gastrointestinal oncologist at Aichi Cancer Center Hospital in Nagoya, Japan. &ldquo;Toxicity profiles were comparable among age subgroups. Quality of life was satisfactory in all age groups in both trials.&rdquo;

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

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 &ge;3) across the age groups.

Reference:

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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