Randomized, Phase II Study Prospectively Evaluating Treatment of Metastatic Esophageal, Gastric, or Gastroesophageal Cancer by Gene Expression of : SWOG S1201.

Purpose: Platinum-based therapy is the standard of care in patients who have HER2-negative, advanced esophagogastric cancer (AEGC). Retrospective data suggest that intratumoral levels may determine platinum sensitivity. A randomized, phase II study was performed in patients with AEGC to explore whether the efficacy of a platinum-based therapy with fluorouracil, leucovorin, and oxaliplatin (FOLFOX) versus a non-platinum-containing regimen of irinotecan and docetaxel (IT) differed according to levels.

Patients And Methods: Overall, 202 untreated patients with HER2-negative AEGC and a Zubrod performance status of 0-1 were evaluated prospectively for mRNA expression of level and then randomly assigned to FOLFOX or IT, stratified by the intratumoral statuses of low (< 1.7) or high (≥ 1.7). Objectives were to assess progression-free survival (PFS) and overall survival (OS) in all patients treated with FOLFOX compared with IT, stratified by low and high levels, and to assess for interactive effects between expression and treatment arm.

Results: Eighty-six percent of patients had values < 1.7. Thus, evaluation of the -high subgroup was limited. Grade ≥ 3 anemia, dehydration, diarrhea, and fatigue were greater in patients with IT. Occurrences of grade ≥ 3 neuropathy and decreased neutrophils were greater in patients with FOLFOX. In all patients, FOLFOX had a statistically superior median PFS compared with IT (5.7 2.9 months; hazard ratio, 0.68; = .02). In patients with levels < 1.7 receiving FOLFOX, PFS and response rate were statistically superior to IT, with no significant difference in OS.

Conclusion: The evaluation of in patients with upper GI tumors was thwarted by an overwhelming predominance of low mRNA expression. Nonetheless, distribution of treatment effects on PFS did not vary with expression. For all patients and for those with low expression, FOLFOX was superior in efficacy to IT.