As reported in the Journal of Clinical Oncology by Iqbal and colleagues, the phase II SWOG S1201 trial showed a progression-free survival benefit with platinum-containing vs nonplatinum treatment among all patients with previously untreated HER2-negative advanced esophagogastric cancer and in a subgroup of patients with low ERCC1 expression. The study was hampered by a very low prevalence of patients with high ERCC1 tumor expression.
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Study Background and Methodology
As noted by the investigators, available data have suggested that lower intratumoral ERCC1 levels are associated with platinum sensitivity and better outcomes with platinum treatment. In SWOG S1201, 202 patients were randomly assigned to receive platinum-based therapy with fluorouracil, leucovorin, and oxaliplatin (FOLFOX; n = 98) vs a non–platinum-containing regimen of irinotecan and docetaxel (n = 104). Randomization was stratified according to high (≥1.7 × 10−3) vs low (all other levels) tumor ERCC1 mRNA expression.
Key Findings
Overall, only 13% of patients in each group had high tumor ERCC1 levels, limiting evaluation of the effect of treatment according to expression level.
The median progression-free survival was 5.7 months in the FOLFOX group vs 2.9 months in the irinotecan/docetaxel group (hazard ratio [HR] = 0.71, P = .02), median overall survival was 11.4 months vs 8.7 months (HR = 0.82, P = .20), and objective response rates in evaluable patients were 42% vs 30% (P = .10).
Among patients with low ERCC1 expression, median progression-free survival was 5.9 months vs 2.8 months (HR = 0.68, P = .02), median overall survival was 11.4 months vs 8.0 months (HR = 0.83, P = .24), and objective response rates were 44% vs 28% (P = .04). Among patients with high ERCC1 expression, median progression-free survival was 4.7 months vs 5.3 months (HR = 0.91, P = .83) and objective response rates were 22% vs 42% (P = .64).
When progression-free survival by treatment group was plotted within ERCC1 expression quartiles, a consistent pattern of benefit for FOLFOX vs irinotecan/docetaxel was observed; since this finding provided little evidence of differential treatment effects across ERCC1 levels, no statistical tests for interaction were performed.
The investigators concluded, “The evaluation of ERCC1 in patients with upper [gastrointestinal] tumors was thwarted by an overwhelming predominance of low ERCC1 mRNA expression. Nonetheless, distribution of treatment effects on [progression-free survival] did not vary with expression. For all patients and for those with low ERCC1 expression, FOLFOX was superior in efficacy to [irinotecan/docetaxel].”
Syma Iqbal, MD, of the University of Southern California Norris Comprehensive Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by grants from the National Cancer Institute. For full disclosures of the study authors, visit ascopubs.org.
