Abstract 3116: MGMT immunohistochemistry (IHC) as a biomarker for response to combination therapy with capecitabine and temozolomide (C/T) in patients (pts) with advanced neuroendocrine carcinomas (aNEC)
Authors: Owen Dwight , Alexander Andrew J. , Wei Lai , Hemminger Jessica , Shah Manisha H. 
Published: July 2016

Introduction: Tumor O6-methylguanine-methyltransferase (MGMT) reverses temozolomide-induced DNA injury, and low MGMT tumor expression has been shown as a predictor of response to temozolomide in glioblastoma. C/T therapy induces partial responses in up to 70% of pts with grade 1-2 pancreatic NEC but the role of MGMT expression as a predictor is unclear. We evaluated MGMT expression by IHC as a prognostic and predictive biomarker for pts with aNEC of all grades and primary sites treated with C/T.

Methods: A retrospective review was carried out at Ohio State University of 29 pts with aNEC who received C/T therapy from 2009 to 2013 and who were evaluable for RECIST response. MGMT expression was assessed when available by IHC on pre-treatment tumor samples to test the hypothesis that low MGMT expression (&lt;10%) predicts response to C/T therapy vs high levels (≥10%).

Results: Of 29 pts, primary NEC site was pancreas in 18 pts, and non-pancreas in 11 pts. Objective response, progression-free survival (PFS) and overall survival (OS) data are outlined in the Table. Partial response (PR) rate was 50% in pts with pancreas primary vs 18% for non-pancreas primary. High PRs were observed in pts with grade 3 NEC (57%). Median PFS in the MGMT-low group was 16.6 months vs 9.5 months in the MGMT-high group (p = 0.19). Median OS in the MGMT low group was 42.9 months vs 18.1 months in the MGMT-high group (p = 0.16). There was a trend toward higher rate of PR (63%) in pts whose tumors had low levels of MGMT expression compared to those with high levels (17%) (p = 0.18).

Conclusion: We observed a trend towards increased PR, median PFS, and median OS in aNEC pts whose tumors had low MGMT protein expression by IHC. The small sample size likely limited the statistical significance of the data. Results of this trial serve as strong rationale for future prospective trials to clarify role of MGMT expression in choosing C/T therapy for pts with NEC. Objective response rate, progression free survival (PFS) and overall survival (OS)N%PR%SD%PDMedian PFSp-valueMedian OSp-valueAll patients2938521013.029.3Low MGMT by IHC (&lt;10%)126238016.60.1942.90.16High MGMT by IHC (≥10%)81767179.518.1Well-differentiated tumor grade (Ki-67 &lt;3%)74357020.00.34NR0.027Moderately differentiated tumor grade (Ki-67 3-20%)13316189.525.9Poorly-differentiated tumor grade (Ki-67 &gt;20%)75714298.413.1

Citation Format: Dwight Owen, Andrew J. Alexander, Lai Wei, Jessica Hemminger, Manisha H. Shah. MGMT immunohistochemistry (IHC) as a biomarker for response to combination therapy with capecitabine and temozolomide (C/T) in patients (pts) with advanced neuroendocrine carcinomas (aNEC). [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3116.