Abstract 5813
Background
Biliary Tract Cancers (BTC) are a devastating and molecularly heterogeneous group of diseases, with significant differences between intrahepatic (ICC) and extrahepatic (ECC) cholangiocarcinoma and Gall bladder (GB) cancer. O6-methylguanine-DNA methyltransferase (MGMT) is a key DNA repair gene, responsible of alkyl groups’ elimination from the O6-position of guanine. Reductions in MGMT expression and MGMT promoter methylation result in diminished DNA-repair of O6-alkylguanine adducts and enhanced sensitivity to alkylating agents, such as temozolomide (TMZ). This alterations have been described in BTC in small reports with variable frequencies. Here we present data on MGMT methylation tested in BTC pts admitted at our center.
Methods
MGMT promoter methylation was studied via methyl specific PCR (EZ DNA Methylation-Gold™ KIT), while protein expression was assessed with immunohistochemistry (IHC). Formalin-fixed paraffin-embedded (FFPE) tissue samples were also examined using Next Generation Sequencing (50 genes “Hotspot Cancer Panel, Ion Torrent®”).
Results
Archived FFPE tissue sections from 100 pts admitted at Fondazione IRCCS Istituto Nazionale dei Tumori of Milan from October 2017 to February 2019 were analyzed. Amongst the 89 samples with adequate tissue, 73% were ICC, 16% were ECC and 8 % were GC. 34 pts (38%) had MGMT promoter methylation, while low/negative MGMT protein expression was found in 45 pts (50%). MGMT methylation was identified in 38% of ICC, 26% of ECC and 62% of GC. As expected, we identified IDH1/2 mutations in 15%, all affected by ICC. Of note, amongst MGMT methylated pts, there were 4 pts (11%) with concomitant IDH1/2 mutations, which are reported to be associated with CpG Island Methylator Phenotype.
Conclusions
MGMT is a prognostic and predictive marker in glioblastomas and there is an increasing evidence in its role in gastrointestinal cancer, with phase II studies showing a response rate of 10% in chemorefractory MGMT- methylated colorectal cancer treated with TMZ. In our single center experience, MGMT methylation was found in 38% of patients with BTC. This data warrant further confirmation, but there is a growing interest in novel targeted therapies exploiting the role of MGMT methylation as a predictive and prognostic biomarker in BTC.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
F. Morano: Honoraria (institution): Servier. F. Pietrantonio: Honoraria (institution), Advisory / Consultancy: Roche; Honoraria (institution), Advisory / Consultancy: Amgen; Honoraria (institution), Advisory / Consultancy: EMD Serono; Honoraria (institution), Advisory / Consultancy: Sanofi; Honoraria (institution), Advisory / Consultancy: Bayer; Honoraria (institution), Advisory / Consultancy: Servier; Research grant / Funding (self): BMS. M. Di Bartolomeo: Honoraria (institution), Advisory / Consultancy: Eli Lilly; Honoraria (institution), Advisory / Consultancy: Servier; Travel / Accommodation / Expenses: Roche. F.G.M. De Braud: Speaker Bureau / Expert testimony: Bayer; Advisory / Consultancy, Speaker Bureau / Expert testimony: BMS; Advisory / Consultancy: Celgene; Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Advisory / Consultancy: Servier; Advisory / Consultancy: Pharm Research Associated; Advisory / Consultancy: Daiichi Sankyo; Advisory / Consultancy, Speaker Bureau / Expert testimony: Ignyta; Advisory / Consultancy, Speaker Bureau / Expert testimony: Amgen; Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Speaker Bureau / Expert testimony: ACCMED; Advisory / Consultancy: Incyte; Advisory / Consultancy: Teofarma; Advisory / Consultancy: Pierre Fabre; Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Advisory / Consultancy: EMD Serono; Speaker Bureau / Expert testimony: Eli Lilly; Speaker Bureau / Expert testimony: AstraZeneca; Speaker Bureau / Expert testimony: Fondazione Menarini; Speaker Bureau / Expert testimony: MSD. All other authors have declared no conflicts of interest.
Resources from the same session
5134 - Early prediction of the platinum-resistant relapse risk using the CA125 modeled kinetic parameter KELIM: a pooled analysis of AGO-OVAR 7 & 9; ICON 7 (AGO/GINECO/ MRC CTU/GCIG trials).
Presenter: OLIVIER COLOMBAN
Session: Poster Display session 2
Resources:
Abstract
4410 - Mirvetuximab soravtansine, a folate receptor alpha (FRa)-targeting antibody-drug conjugate (ADC), in combination with carboplatin and bevacizumab: Initial results from a Phase 1b study in patients (pts) with ovarian cancer
Presenter: David Omalley
Session: Poster Display session 2
Resources:
Abstract
5077 - Response to Pegylated Liposomal Doxorubicin (PLD) and Weekly Paclitaxel (wpac) in Platinum Resistant (PR) Ovarian Cancer (OC) by BRCA mutation status
Presenter: Louise Bremer
Session: Poster Display session 2
Resources:
Abstract
3483 - Impact of prior pegylated liposomal doxorubicin (PLD) treatment in recurrent ovarian cancer (ROC): Sub-group analysis from a randomized, open-label study comparing trabectedin (T) and PLD versus PLD alone in ROC (ET743-OVC-3006)
Presenter: Bradley Monk
Session: Poster Display session 2
Resources:
Abstract
5423 - OCTAVE - A phase I study of enadenotucirev, an oncolytic group B adenovirus, in combination with weekly paclitaxel in platinum-resistant epithelial ovarian cancer
Presenter: Iain McNeish
Session: Poster Display session 2
Resources:
Abstract
1385 - Phase I study of low dose whole abdominal radiation therapy (LDWART) in combination with weekly paclitaxel (wP) for platinum resistant ovarian cancer (PROC)
Presenter: Natalie Ngoi
Session: Poster Display session 2
Resources:
Abstract
2090 - Phase 1b/2a study assessing the safety and efficacy of adding AL3818 (Anlotinib) to standard platinum-based chemotherapy in subjects with recurrent or metastatic endometrial, ovarian or cervical carcinoma
Presenter: David Miller
Session: Poster Display session 2
Resources:
Abstract
1960 - Phase I Study of Intraperitoneal TRX-E-002-1 in Subjects with Persistent or Recurrent Ovarian, Fallopian Tube or Primary Peritoneal Cancer: Three-month Follow-up Results of the Dose Escalation Phase
Presenter: Jermaine Coward
Session: Poster Display session 2
Resources:
Abstract
4288 - Hybrid capture-based genomic profiling of circulating tumor DNA (ctDNA) from patients with ovarian cancer
Presenter: Mi Yang
Session: Poster Display session 2
Resources:
Abstract
3433 - Tumor Microvessel Density for predicting Nintedanib activity: data from the randomized CHIVA trial (a GINECO study)
Presenter: Maud Villemin
Session: Poster Display session 2
Resources:
Abstract