Effect of TP53 mutation status on survival in the MAGIC trial.

Authors

null

Elizabeth Catherine Smyth

Royal Marsden NHS Foundation Trust, London and Surrey, United Kingdom

Elizabeth Catherine Smyth , Sanna Hulkki Wilson , Matthew Guy Nankivell , David Gonzalez de Castro , Andrew Wotherspoon , Alicia Frances Clare Okines , Ruth E Langley , Sally Patricia Stenning , David Cunningham

Organizations

Royal Marsden NHS Foundation Trust, London and Surrey, United Kingdom, Medical Research Council Clinical Trials Unit at University College London, London, United Kingdom

Research Funding

No funding sources reported

Background: In oesophagogastric cancer TP53 mutation may be prognostic and/or predict for chemoresistance, however available data are conflicting. We hypothesised that TP53 status would impact on survival for patients (pts) randomised to surgery alone or perioperative ECF chemotherapy in the MRC MAGIC trial. Methods: Genomic DNA FFPE tissue sections were extracted with QIAmp DNA FFPE Tissue Kit (Qiagen, Hilden, Germany). Mutations in exons 4-9 were screened for by fluorescent PCR -amplification of genomic DNA, followed by Capillary Electrophoresis-Single Strand Conformational Analysis (CE-SSCA). Mutations were characterised by bi -directional Sanger sequencing analysis performed on an independent PCR -reaction and the sequencing results were compared to the reference sequences in the COSMIC database. TP53 status was correlated with demographics and survival. Results: TP53 results were available on 154 pts (50% of pts with available DNA). The remainder failed CE-SSCA due to degraded DNA. Pts with/without TP53 data had similar demographics and survival. TP53 mutation was detected in 51/154 (33%) samples. Exon 4, 5, 6, 7 and 8 mutations occurred in 4%, 42%, 8%, 36% and 10% of specimens with a TP53 result. Pts with TP53 mutations were more likely to have an oesophageal or junctional tumor (vs. gastric) than TP53 wild type (WT) pts (38% vs. 17% respectively p = 0.016). Survival from surgery was comparable for pts with mutant and WT TP53 tumors in both arms of the trial (See Table). P-value for interaction between treatment group and TP53 status was 0.776, indicating no interaction was present. Conclusions: In the MAGIC trial, TP53 mutation status was not prognostic, and did not predict for lack of benefit from chemotherapy. Further study is required in order to evaluate the effect of differing TP53 mutations on treatment and survival.

Effect of TP53 status on survival in chemotherapy and surgery pts in MAGIC.

Chemotherapy patients
Surgery patients
All patients
TP53WTTP53MutTP53WTTP53MutTP53WTTP53Mut
Patients5419493210351
Events391237207632
Median OS (years)1.12
(0.61, 1.86)
1.05
(0.68, NA)
1.71
(1.37, 2.40)
1.48
(1.05, 4.13)
1.60
(1.16, 2.31)
1.46
(0.98, 2.60)
HR
95% CI
0.86
(0.45, 1.65)
0.99
(0.57, 1.71)
0.92
(0.61, 1.39)
p-value0.65650.96820.6766

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Abstract Details

Meeting

2015 Gastrointestinal Cancers Symposium

Session Type

Poster Session

Session Title

General Poster Session A: Cancers of the Esophagus and Stomach

Track

Cancers of the Esophagus and Stomach

Sub Track

Translational Research

Citation

J Clin Oncol 33, 2015 (suppl 3; abstr 71)

DOI

10.1200/jco.2015.33.3_suppl.71

Abstract #

71

Poster Bd #

B21

Abstract Disclosures

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