Abstract 3339
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 in MNR group 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.
Clinical trial identification
Australian New Zealand Clinical Trials Registry: 12609000665235.
Legal entity responsible for the study
The Australasian Gastro-Intestinal Trials Group (AGITG).
Funding
The National Health and Medical Research Council, Australia.
Editorial Acknowledgement
No editorial assistance was accessed for this abstract.
Disclosure
All authors have declared no conflicts of interest.