Long term results and patterns of recurrence from SCOPE 1: A phase II/III randomised trial of definitive chemoradiotherapy (dCRT) plus or minus cetuximab (dCRT+C) in esophageal cancer.

Abstract

118 Background: One of the largest trials in dCRT for localised oesophageal cancer, SCOPE 1 tested the role of adding cetuximab to conventional dCRT, and showed that this was associated with greater toxicity and worse survival. Here we present the long-term outcomes. Methods: Phase II/III trial. Randomisation: cisplatin 60mg/m2 D1 and capecitabine 625mg/m2 daily D1-21 for 4 cycles with/without Cetuximab 400mg/m2 D1 followed by 250mg/m2weekly. RT: 50Gy in 25 fractions given concurrent with cycles 3 and 4. Recruitment: Feb 2008 - Feb 2012, when the IDMC recommended trial closure on the basis of futility. Results: 258 patients (dCRT = 129; dCRT+C = 129) were recruited from 36 centres. Median follow-up (IQR): 46.7 (36.0-49.0) months for all surviving pts. 65.1% (dCRT arm) and 69.8% (dCRT+C arm) of patients had died. Esophageal cancer was the cause in 82.1% and 86.7% of deaths respectively (p = 0.41). Median OS months (95% CI) was 34.5 (24.7-42.3) in dCRT and 24.7 (18.6-31.3) in dCRT+C (HR 1.25, p = 0.137); corresponding 3-year OS (95% CI) was 47.2% (38.2%-55.7%) and 37.6% (29.1%-46.0%). Median PFS (95% CI): 24.1 (15.3-29.9) and 15.9 (10.7-20.8) months respectively (HR1.28, p = 0.114). There was some evidence that local PFS (within RT field) was lower in the dCRT+C arm (HR1.38, p = 0.051). On multivariable analysis including treatment arm, Stage I-II ds (vs Stage III), full-dose RT and higher cisplatin dose intensity ( ≥ 75% vs < 75%) were associated with improved OS and PFS. Patterns of recurrence (n [%]) were similar in both arms (see table). In dCRT arm, 31/38 pts (81.6%) with local relapse within the RT field compared to 40/48 (83.3%) in the dCRT+C arm (p = 0.8). Conclusions: The mature analysis shows unprecedented survival in dCRT arm, comparable to surgical trials (e.g. 3-year OS % [95% CIs] in OE05: CF 39 [35, 44] and ECX 42 [37, 46], in OE02: 31 [27, 36]). OS inferiority of dCRT+C is no longer statistically significant. The lower PFS (within RT field) in the dCRT+C arm was consistent with the lower number of patients receiving full dose of RT in the dCRT+C arm. Clinical trial information: 47718479. [Table: see text]