Progression-free survival and recurrence results for AGITG DOCTOR: Pre-op cisplatin, 5FU & DOCetaxel +/-radiotherapy after poor early response to cisplatin & 5FU for resectable oesophageal adenocarcinoma

Abstract

Background: Resectable oesophageal and gastro-oesophageal junction adenocarcinoma patients (pts) without early metabolic response (EMR) to chemotherapy as defined by 18-FDG-PET (PET) show poor survival and major histological response rates (RR) <5%. This multicentre trial previously reported changing neoadjuvant therapy improved major histological RR for early metabolic non-responders (MNR). Grade 3/4 toxicities were seen in 27% of pts on 5-FU + cisplatin (CF); 42% on docetaxel+ CF (DCF) and 71% on DCF + concurrent 45Gy radiotherapy (DCFRT). Updated results now report progression-free survival (PFS) and local recurrence. Methods: Pts had a day 15 PET scan after induction CF. Early metabolic responders (SUVmax decreasing by≥ 35% from baseline to day 15 PET) received a 2nd CF cycle then oesophagectomy. Early metabolic non-responders were centrally randomised 1:1 to 2 cycles of DCF or DCFRT then oesophagectomy. Primary endpoint was major histological RR (<10% residual tumour). Seconday endpoints were PFS and local recurrence. Results: From 2009 -2016, 124 pts were recruited. 45 were deemed early metabolic responders. 77 were deemed early metabolic non-responders and 31 allocated DCF and 35 to DCFRT. 11 were not randomised (progression, toxicity, refusal). 2 were not evaluable. Major histological response rates: 7% EMR (CF); 20% DCF; 63% DCFRT. Local recurrence: 5/45 (11%) EMR (CF); 10/31 (32%) MNR allocated DCF; 4/35 (11%) MNR allocated DCFRT. PFS at 36m: 46% (95% CI 31-60%) for EMR; 31% (95% CI 16-48%) for MNR allocated DCF; 46% (95% CI 29- 61%)MNR allocated to DCFRT. Conclusions: Early metabolic response to CF alone is associated with favourable PFS and low local recurrence rate despite a low major histological RR. The addition of docetaxel inMNRgroup may augment histological RR but PFS ≈ local recurrence outcomes remained inferior. Further addition of RT to DCF produced the highest histological RR and PFS/local recurrence outcomes matching EMR group. Early PET can enable tailoring of therapy to 'close the gap' in outcomes between early metabolic response and early metabolic non-response patients.