Induction oxaliplatin capecitabine followed by switch to carboplatin-paclitaxel based RT versus continuing oxaliplatin capecitabine RT in operable esophageal adenocarcinoma: Survival analysis of the randomized phase II neoscope trial

Abstract

Background: Initial results of the NEOSCOPE trial comparing pre-operative CarPac vs OxCap based chemoradiotherapy (CRT) in patients with adenocarcinoma of the oesophagus or oesophagogastric junction showed comparable toxicity and improvement in pathological complete response (pCR) in favour of the CarPacRT. Here we report survival after a median follow-up of 40.7 months (95% CI: 45.1-53.6). Methods: NEOSCOPE was an open, randomised, 'pick a winner' phase II trial. Patients with resectable oesophageal adenocarcinoma ' cT3 and/or ' cN1 were randomised to OxCapRT (oxaliplatin 85 mg/m2 day 1, 15, 29; capecitabine 625 mg/m2 bd on days of RT) or CarPacRT (carboplatin AUC2; paclitaxel 50 mg/m2 day 1, 8, 15, 22, 29). RT dose was 45 Gy/25 fractions/5 weeks. Induction OxCap (2 cycles) was given prior to CRT. Surgery was performed 6'8 weeks after CRT.The primary endpoint was pCR, secondary endpoints were toxicity, PFS and OS. Results: Between Oct 2013 and Feb 2015, 85 patients were recruited from 17 UK centres. Median OS was not reached in the CarPacRT group and was 41.72 months (95% CI 19.58-.)in the OxCap group (HR 0.56[95% CI 0.29-1.07]; p=0.079). 3-year and 5-year OS rates were 74% (95% CI 58%-85%) and 54% (95% CI 34%-71%) (CarPacRT), and 52% (95% CI 35%-67%) and 39% (95% CI 21%-56%) (OxCapRT). Median PFS (not reached vs 35.3 months, HR=0.61 [95% CI 0.33-1.12]; p=0.111) and metastatic PFS (not reached vs 39.0 months, HR=0.61 [95% CI 0.32-1.14], p=0.118) both favoured the CarPacRT arm. Local recurrence rate was low (OxCapRT= 10%; CarPacRT= 7%). The OS benefit for CarPacRT was consistent across subgroups but not statistically significant. Conclusions: In this longer term analysis there was some evidence that induction OxCap followed by switch to CarPacRT was superior to continuing OxCapRT, with efficacy similar to that seen in other published studies such as 'CROSS' and 'FLOT?. Taken together with the previously published pCR results CarPacRT rather than OxCapRT warrants inclusion in future trials. Funding: Cancer Research UK (C44694/A14614). Clinical trial information: NCT01843829.