Outcomes of ERCC1 high locally advanced esophageal cancer patients treated with non-platinum vs platinum based CRT.

Abstract

192 Background: ERCC1 is a DNA excision repair enzyme which repairs the DNA adduct damage caused by platinum and hence high levels of ERCC1 has been associated with platinum resistance. Thus utility of platinum as a first line chemotherapy in esophageal cancers with high ERCC1 levels is controversial. SWOG S0356 trial noted a significantly low 2 year overall survival of 37% for platinum based CRT in ERCC1 high esophageal carcinomas, yet no studies have identified the alternative first line chemotherapy. Our Program utilized combined irinotecan 65mg/m2 on D1 and D8 and nab-paclitaxel 100mg/m2with concurrent radiation therapy of 50.4Gy for ERCC1 high esophageal cancers at the treating physician’s discretion. We compared the differences in survival with non-platinum versus platinum CRT. Methods: Retrospective analysis from 2011 to 2016 identified 25 locally advanced esophageal cancer patients in whom ERCC1 levels were checked. Out of this 25 patients 23 had high ERCC1 levels and 2 had low ERCC1 levels. Patients with low ERCC1 were excluded. Patients with high ERCC1 levels received either non-platinum or platinum CRT as neo-adjuvant, adjuvant or definitive chemotherapy. Results: Patient characteristics: Male 69.5%, female 30.5%, squamous 43.4%, adenocarcinoma 52.1%, other 4.5%, operable 39%, non-operable 61%. Non-platinum therapy was utilized for 69.5% and platinum based therapy for 30.5% of the patients. Kaplan-Meier analysis for survival showed clear separation of the curves around 2 years. Median overall survival of non-platinum doublet was not reached during a median follow up of 22 months. Overall survival at 2 years was 57%. The median overall survival for the platinum doublet was 22 months and the 2 year overall survival was 42%. (p = 0.22). Hazard ratio (HR) 0.48(95% CI 0.14-1.58 p = 0.23) .This statistical non significance was due to small sample size. Conclusions: Abraxane and irinotecan showed improved overall survival in the ERCC1 high group when compared with platinum based therapy demonstrated both in our population and the SWOG 0356 trial. [Table: see text]