Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Poster display session

3196 - Selecting patients with metastatic colorectal cancer for treatment with temozolomide using proteomic analysis of MGMT

Date

11 Sep 2017

Session

Poster display session

Presenters

Sarit Schwartz

Citation

Annals of Oncology (2017) 28 (suppl_5): v22-v42. 10.1093/annonc/mdx363

Authors

S. Schwartz1, F. Cecchi1, Y. Tian1, K. Scott1, M. Di Bartolomeo2, F. Morano2, G. Fucà2, A. Martinetti2, F. De Braud2, F. Dominoni2, M. MILIONE2, M.A. Calegari3, A. Orlandi3, C. Barone4, F. Pietrantonio2, T. Hembrough1

Author affiliations

  • 1 R&d, NantOmics, LLC, 20850 - Rockville/US
  • 2 Department Of Medical Oncology, Fondazione IRCCS - Istituto Nazionale dei Tumori, 20133 - Milano/IT
  • 3 Department Of Medical Oncology, Policlinico Universitario A. Gemelli, 00168 - Roma/IT
  • 4 Department Of Medical Oncology, Università Cattolica del Sacro Cuore, 20123 - Milano/IT
More

Resources

Abstract 3196

Background

Temozolomide (TMZ) is a standard treatment for melanoma and glioblastoma and it has shown limited but encouraging activity in patients with metastatic colorectal cancer (mCRC). In multiple cancer types, the DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) is a resistance marker for TMZ; MGMT promoter methylation is associated with loss of MGMT expression and response to TMZ. We hypothesized that mCRC patients whose tumors expressed quantities of MGMT protein below a pre-defined cutoff would have better outcomes on TMZ than patients with MGMT expression above the cutoff. To test our hypothesis, we assessed MGMT by mass spectrometry in the tumor samples of patients with refractory mCRC and MGMT promoter methylation receiving TMZ.

Methods

Archived formalin-fixed, paraffin-embedded tissue sections were obtained from 24 patients from two phase 2 trials. A pathologist marked the tumor areas, which were microdissected and solubilized. In each tumor sample, multiple protein biomarkers including MGMT were quantified with selected reaction monitoring mass spectrometry. An MGMT cutoff of 200 amol/ug was based on the limit of quantitation from a concentration curve. The Mantel-Cox log-rank and the Fisher’s exact tests were used for survival comparisons.

Results

MGMT protein was detected in 13 of 24 (54.2%) colorectal tumor samples (range: 229.3-784.8 amol/µg). The overall response rate was 29%. Patients with MGMT protein levels below a cutoff of 200 amol/ug (n = 11) had a notably higher response rate than patients with MGMT levels above the cutoff (64% vs. 0%; p = 0.001 Fisher’s test). Also a longer progression-free survival was observed (4.3 vs. 1.6 months, HR = 0.36, 95% CI = 0.13-1.10, p = 0.054). Results for overall survival were consistent but not statistically significant (8.9 vs 6.9 months, HR = 0.55, p = 0.221).

Conclusions

Patients with mCRC whose tumors expressed low or undetectable levels of MGMT protein had better outcomes following TMZ treatment than their counterparts. Quantitative proteomic analysis of MGMT could potentially be used to select CRC patients for TMZ treatment. The results of validation studies are forthcoming.

Clinical trial identification

Legal entity responsible for the study

NantOmics

Funding

NantOmics

Disclosure

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

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.