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Poster display session

4660 - ATM loss, MSI and survival in the MAGIC trial

Date

09 Sep 2017

Session

Poster display session

Presenters

Elizabeth Smyth

Citation

Annals of Oncology (2017) 28 (suppl_5): v209-v268. 10.1093/annonc/mdx369

Authors

E. Smyth1, M. Fassan2, K. Kouvelakis3, M. Nankivell4, C. Peckitt3, A. Wotherspoon5, N. Valeri6, M. Rugge2, W. Allum7, R. Langley4, D. Cunningham1

Author affiliations

  • 1 Gastrointestinal Oncology, Royal Marsden Hospital, SW3 6JJ - London/GB
  • 2 Department Of Medicine, University of Padua, Padua/IT
  • 3 Clinical Research & Development, Royal Marsden Hospital, SM2 5PT - Sutton/GB
  • 4 Clinical Trials Unit, Medical Research Council at University College London, WC1E6BT - London/GB
  • 5 Pathology, Royal Marsden Hospital, SW3 6JJ - London/GB
  • 6 Molecular Pathology, The Institute of Cancer Research/Royal Marsden Hospital, SM2 5NG - Sutton/GB
  • 7 Surgery, Royal Marsden Hospital, SW3 6JJ - London/GB
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Resources

Abstract 4660

Background

Loss of ataxia-telangiectasia mutated (ATM) protein has been associated with worse prognosis in resected gastric cancer (GC), and may predict sensitivity to drugs targeting DNA damage pathways. Microsatellite instability (MSI) is prognostic in surgically treated GC patients (pts) and may be negatively prognostic in perioperative chemotherapy (chemo) treated GC. We examined the effect of ATM and MSI on overall survival (OS) for pts randomised to surgery alone or perioperative ECF chemo in the MRC MAGIC trial.

Methods

ATM was assessed using anti-ATM antibody (clone Y170) on 4 µm TMA sections. ATM negative (neg) tumours had >90% cells neg for nuclear ATM. MSI was assessed using Promega MSI System. MSS tumours had all markers stable; MSI-L had only 1 unstable marker; MSI-H had at least 2 unstable markers. Trial arms were analysed independently.

Results

39 of 225 evaluated pts (17%) were ATM-neg. Pts with/without ATM data had similar OS. Clinicopathological characteristics were similar between ATM-neg and positive (pos) pts. 217 pts had MSI and ATM status available: MSI and ATM status were highly correlated (ATM-neg/MSS n = 27, ATM neg/MSI-H n = 10, ATM-pos/MSS n = 175, ATM-pos/MSI-H n = 5, p 

Conclusions

In MAGIC, ATM status was not prognostic for OS in either treatment arm. ATM loss was much more common in MSI-H pts. In this relatively underpowered analysis, chemo treated MSS-ATM-neg pts had encouraging OS. In chemo treated pts, prognosis was poor for MSI-H patients independent of ATM status. Further evaluation of ATM, MSI and chemo outcomes may be justified.

Clinical trial identification

Not applicable

Legal entity responsible for the study

Medical Research Council

Funding

Cancer Research UK grant C20023/A7217

Disclosure

E. Smyth: Honoraria for advisory role: Five Prime Therapeutics, Bristol-Meyer Squibb. C. Peckitt: Honoraria for consulting or advisory role from Sanofi. W. Allum: Honoraria from Nestle and Lilly. D. Cunningham: Research funding: Amgen, AstraZeneca, Celgene, MedImmune, Merck Serono, Merrimack, Sanofi. All other authors have declared no conflicts of interest.

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