A randomized phase II pilot study prospectively evaluating treatment for patients based on ERCC1 for advanced/ metastatic esophageal, gastric, or gastroesophageal junction cancer: SWOG S1201.

Abstract

4009 Background: Platinum based treatment (tx) is standard in HER2 negative patients (pts) with advanced esophagogastric cancer (AEGC). Retrospective data suggest intratumoral ERCC1 levels may determine platinum sensitivity. A randomized phase II study was performed in pts with AEGC to explore whether the efficacy of a platinum 5-FU/LV/Oxaliplatin (FOLFOX) vs. non-platinum containing regimen irinotecan/taxotere (IT) differed according to ERCC1 levels. Methods: 203 untreated pts with AEGC, Her2 -, Zubrod PS 0-1, were randomized to FOLFOX vs. IT, stratified by intratumoral ERCC1 low (<1.7) vs. high (≥1.7). Objectives were to assess PFS and OS in all pts treated with FOLFOX compared with IT, and in those pts with low and high ERCC1 levels and to assess for interactive effects between ERCC1 expression and tx arm. Results: 86% of pts had ERCC1 values <1.7. Thus, evaluation of ERCC1 pts in the high subgroup was not feasible. Tx groups were well matched by age, sex, race, ERCC1 level, and site. A series of K-M plots were used to explore whether tx arm differences in PFS varied based on ERCC1 levels; little evidence of such was noted. Grade ≥ 3 anemia, dehydration, diarrhea and fatigue were greater in pts with IT. Grade ≥ 3 neuropathy and decreased neutrophils were greater in pts with FOLFOX. Conclusions: In all pts, FOLFOX had a statistically superior PFS and RR, when compared with IT. In pts with ERCC1 <1.7 receiving FOLFOX, PFS and RR was statistically superior, with no difference in OS. There was no significant evidence of differential treatment effect on PFS across ERCC1 levels. Clinical trial information: NCT01498289. [Table: see text]