146P - Predicting response to chemotherapy in gastric cancer patients randomized to docetaxel: a reevaluation of the ITACA-S trial

Date 11 September 2017
Event ESMO 2017 Congress
Session Poster display session
Topics Anti-Cancer Agents & Biologic Therapy
Cancer in Adolescents
Gastric Cancer
Translational Research
Presenter Fabiola Cecchi
Citation Annals of Oncology (2017) 28 (suppl_5): v22-v42. 10.1093/annonc/mdx363
Authors F. Cecchi1, D.V. Catenacci2, S. Schwartz1, S. Sellappan1, Y. Tian1, R. Miceli3, F. Pietrantonio4, A. Pellegrinelli5, A. Martinetti3, M. Di Bartolomeo3, T. Hembrough1
  • 1R&d, NantOmics, LLC, 20850 - Rockville/US
  • 2Department Of Medical Statistics, Biometry, And Bioinformatics, University of Chicago Medicine, 60637 - Chicago/US
  • 3Department Of Medical Oncology, Fondazione IRCCS - Istituto Nazionale dei Tumori, 20133 - Milano/IT
  • 4Department Of Medical Oncology, Fondazione IRCCS - Istituto Nazionale dei Tumori, 20850 - Milano/IT
  • 5Pathology And Laboratory Medicine,, Fondazione IRCCS - Istituto Nazionale dei Tumori, 20133 - Milano/IT

Abstract

Background

No predictive biomarker for chemotherapy has been validated for clinical use. Clinical studies suggest tumor expression of the proteins class III β-tubulin (TUBB3) and thymidine phosphorylase (TYMP) predict resistance to taxane and response to 5-FU, respectively. Immunohistochemical definitions of protein status vary widely. We evaluated relationships between survival and expression of TUBB3 and TYMP as quantitated by mass spectrometry in the archived tumor samples of 247 patients from the Intergroup Trial of Adenocarcinoma of the Stomach (ITACA-S). Patients had been randomized to monotherapy with 5-FU/LV or to FOLFIRI plus docetaxel and cisplatin.

Methods

Gastric tumor tissues were microdissected and solubilized for proteomic quantitation of 45 protein biomarkers. The cutoff for TUBB3 (750 amol/µg of total protein) was predetermined based on the assay’s limit of detection. An experimental cutoff for TYMP (1335 amol/ug) was derived in the 5-FU/LV-treated patients using Monte Carlo 2-fold cross-validation. The Mantel-Cox log-rank test was used for survival comparisons.

Results

Among gastric cancer (GC) patients treated with docetaxel-containing chemotherapy (n = 125), those with TUBB3 protein levels below the cutoff had a longer median overall survival (mOS) than patients with TUBB3 levels above the cutoff (1563 vs 886 days, p 

Conclusions

Quantitative proteomic analysis identified subsets of trial patients who benefitted from specific adjuvant chemotherapy regimens. Personalized chemotherapy based on quantitated TYMP and TUBB3 is promising and warrants broader evaluation.

Clinical trial identification

ClinicalTrials.gov Identifier:

Legal entity responsible for the study

NantOmics, LLC

Funding

IRCCS and NantOmics, LLC

Disclosure

F. Cecchi, S. Schwartz, S. Sellappan, T. Hembrough, Y. Tian: Employee at NantOmics. All other authors have declared no conflicts of interest.