Efficacy of Sequential Ipilimumab Monotherapy vs Best Supportive Care For Unresectable Locally Advanced/Metastatic Gastric or Gastroesophageal Junction Cancer

Purpose: Ipilimumab, a monoclonal antibody that blocks cytotoxic T-lymphocyte-associated protein-4 interactions, enhances T-cell activation and promotes tumor immunity. This phase 2 study evaluated the safety and efficacy of ipilimumab monotherapy vs best supportive care among patients with advanced/metastatic gastric or gastroesophageal junction cancer who achieved at least stable disease with first-line chemotherapy.<br /><br />Experimental Design: Eligible patients were randomized to ipilimumab 10 mg/kg every 3 weeks for four doses, then 10 mg/kg every 12 weeks for up to 3 years, or BSC, which could include continuation of fluoropyrimidine until progression or toxicity. The primary endpoint was immune-related progression-free survival (irPFS); secondary endpoints included PFS by modified WHO criteria and overall survival (OS). <br /><br />Results: Of 143 patients screened, 57 were randomized to each arm. irPFS with ipilimumab vs BSC was not improved (2.92 months [95% CI, 1.61-5.16] vs 4.90 months [95% CI, 3.45-6.54], HR=1.44; 80% CI, 1.09-1.91; P=0.097), resulting in study cessation. At study closeout, which occurred 8 months after the interim analysis, the median OS durations were 12.7 months (95% CI, 10.5-18.9) and 12.1 months (95% CI, 9.3-not estimable), respectively. Grade 3/4 treatment-related adverse events (TRAEs) occurred in 23% of ipilimumab-treated patients, of which diarrhea (9%) and fatigue (5%) were most frequent, and in 9% of active BSC-treated patients. <br /><br />Conclusions: While ipilimumab at 10 mg/kg was manageable it did not improve irPFS vs BSC. However, comparable median OS of »1 year and a favorable safety profile support the investigation of ipilimumab in combination with other therapies for advanced gastric cancer.

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