610O - An AGITG trial –A randomised phase II study of pre-operative cisplatin, fluorouracil and DOCetaxel +/-radioTherapy based on poOR early response to...

Date 08 October 2016
Event ESMO 2016 Congress
Session Gastrointestinal tumours, non-colorectal 1
Topics Anticancer agents
Oesophageal Cancer
Surgical Oncology
Therapy
Biological Therapy
Radiation Oncology
Presenter Andrew Barbour
Citation Annals of Oncology (2016) 27 (6): 207-242. 10.1093/annonc/mdw371
Authors A. Barbour1, E. Walpole2, G..T. Mai3, H. Chan4, E. Barnes4, D. Watson5, S. Ackland6, V. Wills7, J. Martin8, M. Burge9, C. Karapetis10, J. Shannon11, L. Nott12, V. Gebski4, K. Wilson4, J. Thomas13, G. Lampe14, J. Zalcberg15, J. Simes4, M. Smithers16
  • 1Department Of Surgery, Princess Alexandra Hospital, 4102 - Brisbane/AU
  • 2Medical Oncology, Princess Alexandra Hospital, 4102 - Brisbane/AU
  • 3Radiation Oncology, Princess Alexandra Hospital, Brisbane/AU
  • 4Nhmrc Clinical Trials Centre, University of Sydney, Sydney/AU
  • 5Oesophago-gastric Surgical Unit, Flinders Medical Center, 5042 - Bedford Park/AU
  • 6Medical Oncology, Calvary Mater Hospital Newcastle, Newcastle/AU
  • 7Division Of Surgery, John Hunter Hospital, Newcastle/AU
  • 8Radiation Oncology, Calvary Mater Hospital Newcastle, Newcastle/AU
  • 9Medical Oncology, Royal Brisbane and Women's Hospital, Herston/AU
  • 10Department Of Medical Oncology, Flinders Medical Center, 5042 - Bedford Park/AU
  • 11Medical Oncology, Nepean Cancer Care Centre, 2747 - Kingswood/AU
  • 12Medical Oncology, Royal Hobart Hospital, Hobart/AU
  • 13Mater Medical Centre, Princess Alexandra Hospital, Brisbane/AU
  • 14Pathology Queensland, Princess Alexandra Hospital, Brisbane/AU
  • 15Epidemiology And Preventative Medicine, Monash University, The Alfred Hospital, Melbourne/AU
  • 16The University Of Queensland, Princess Alexandra Hospital, Brisbane/AU

Abstract

Background

Patients (pts) with esophageal/ gastro-esophageal junction (GOJ) adenocarcinoma (EAC) who do not show early metabolic response (as defined by 18-FDG PET) to chemotherapy have poorer survival and histological response rates

Methods

Pts with resectable EAC were enrolled to a multicentre randomised phase II trial. PET scans were performed at baseline and after receiving one cycle of cisplatin and fluorouracil (CF) (day 15). If SUVmax decreased by ≥ 35%, pts were classified as early metabolic responders (EMR), otherwise as non-metabolic responders (NMR). EMR pts continued with a 2nd cycle of CF follow by surgery while the NMR pts were randomised 1:1 to receive either CF and docetaxel (DCF) for two cycles, or DCF concurrent with 45Gy radiotherapy (DCFRT). The primary endpoint was histological response (

Results

124 pts were enrolled (62% esophagus and 38% GOJ) and received one cycle of CF. At day 15, 45/122 (37%) pts were EMR and 77/122 (63%) were NMR and 2 did not have a day 15 PET. Of the NMR group, 31 were randomised to DCF; 35 to DCFRT; 11 were not randomised (2 pts progressed, 4 had toxicities and 5 refused). Grade 3 or 4 toxicities (AE) were seen in 19/58 (33%) pts on CF, 14/31 (45%) DCF pts and 25/35 (71%) DCFRT pts. No treatment related deaths were seen. Esophagectomy was performed in 45 (100%) EMR, 28/31 (90%) DCF (1 refused DCF, 1 refused surgery and 1 AE) and 33/35 (94%) DCFRT (2 progressed). R0 (>1mm margin) resection was achieved in 31/45(69%) of EMR, 18/28 (64%) of DCF, 31/33 (94%) of DCFRT pts. A major histological response was achieved in 3/45 (7%) EMR pts, 6/30 (20%) DCF pts, and 22/35 (63%) DCFRT pts.

Conclusions

Docetaxel added to CF, particularly DCFRT, can induce high rates of histological responses in NMR pts. Therefore tailoring multimodality therapy based on individual PET response is safe and feasible in EAC, although the impact on survival requires longer follow up.

Clinical trial identification

The Australian New Zealand Clinical Trials Registry (ANZCTR)- ACTRN12609000665235

Legal entity responsible for the study

Australasian Gastro-Intestinal Trials Group

Funding

National Health & Medical Research Council (NHMRC) Project Grant (Application ID 1011782) and Sanofi-Aventis Australia pty limited

Disclosure

L. Nott: Advisory Board Roche, MSD. All other authors have declared no conflicts of interest.