Iqbal S, McDonough S, Lenz HJ, et al. - For patients who have HER2-negative, advanced esophagogastric cancer (AEGC), the standard of care comprised platinum-based therapy. Given the proposed value of intratumoral ERCC1 levels for determining platinum sensitivity, a randomized, phase 2 study was undertaken in cases with AEGC to explore whether the efficacy of a platinum-based therapy with fluorouracil, leucovorin, and oxaliplatin (FOLFOX) vs a non–platinum-containing regimen of irinotecan and docetaxel (IT) differed according to ERCC1 levels. Researchers determined mRNA expression of ERCC1 level in 202 untreated patients with HER2-negative AEGC and a Zubrod performance status of 0-1 and then randomly assigned them to receive FOLFOX or IT, stratified by the intratumoral statuses of ERCC1 low (< 1.7) or high (≥ 1.7). ERCC1 values < 1.7 were evident in 86% of patients. This overwhelming predominance of low ERCC1 mRNA expression in patients with upper GI tumors thwarted the evaluation of ERCC1. Nonetheless, there was no variation in the distribution of treatment effects on progression-free survival with expression. Outcomes support the superiority of FOLFOX in efficacy to IT for all patients and for those with low ERCC1 expression.