Abstract 1894
Background
Locally advanced pancreatic adenocarcinoma (LAPC) is treated similarly to metastatic pancreatic cancer (MPC). It has previously been thought that SMAD4 is wildtype (WT) in LAPC. We describe results of whole genome (WGS) and RNA sequencing (RNAseq) of LAPC and MPC tumours.
Methods
Patients with LAPC and MPC were enrolled in the COMPASS clinical trial (NCT02750657). Clinical, demographic and survival data were collected. WGS and RNAseq was performed along with modified Moffitt classification (basal-like or classical).
Results
Patients with LAPC (n = 27) and MPC (n = 163) did not differ in terms of age, gender or smoking status. Patients with LAPC had lower BMI (p = 0.005) than those with MPC. More LAPC patients received FOLFIRINOX than those with MPC (p = 0.003). LAPC/MPC tumours had similar rates of KRAS, p53, CDKN2A and SMAD4 mutations and similar levels of ploidy, indels, neoantigens and single nucleotide variants. There was a slight increase in structural variants in MPC vs. LAPC (p = 0.05). No LAPC tumours were homologous recombination deficient (HRD) or KRAS WT, compared with 10 MPC (HRD) and 15 MPC (KRAS-WT). LAPC patients with SMAD4 mutations had higher baseline Ca19.9 than those with WT SMAD4 (p = 0.0048). All LAPC were Moffitt classical subtype on RNAseq, compared with 77% of MPC (p = 0.0049). LAPC patients had improved OS compared with MPC patients on univariate analysis (p = 0.04) but not on multivariate analysis. There was no difference in OS between LAPC and classical subtype MPC, or between LAPC patients with/without SMAD4 mutations.
Conclusions
Patients with LAPC have a similar molecular profile to those with MPC with similar rates of altered drivers including SMAD4. LAPC tumours are more likely to be Moffitt classical subtype and have similar OS to classical subtype MPC. LAPC patients with SMAD4 mutations had similar OS to those with WT SMAD4. These data suggest that patients with LAPC should be treated similarly to those with classical-subtype MPC.
Clinical trial identification
NCT02750657.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Government of Ontario, Wallace McCain Centre for Pancreatic Cancer, Princess Margaret Cancer Foundation, Canadian Cancer Society Research Institute Grant (702316), Pancreatic Cancer Canada Foundation, Canadian Friends of the Hebrew University (Alex U. Soyka), Lebovic Chair in Hepatobiliary/Pancreatic Surgical Oncology.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
4290 - Characterization of the mechanism of action and efficacy of MEN1611 (PA799), a novel PI3K inhibitor, in breast cancer preclinical models.
Presenter: Alessio Fiascarelli
Session: Poster Display session 3
Resources:
Abstract
2167 - Neat-1: culprit lnRNA tying PIG-C, MSLN, CD80 in TNBC
Presenter: Nada Hussein
Session: Poster Display session 3
Resources:
Abstract
1829 - A novel RAF/MEK inhibitor CH5126766 in phase 1 clinical trial has an effectiveness in the combination with eribulin for the treatment of triple negative breast cancer
Presenter: Hisako Ono
Session: Poster Display session 3
Resources:
Abstract
4357 - Identification of a stemness-related gene panel associated with BET inhibition in triple negative breast cancer
Presenter: Eva Galan-Moya
Session: Poster Display session 3
Resources:
Abstract
5163 - Preclinical Evaluation targeting both IGF1R and IR in Triple Negative Breast Cancer
Presenter: Alex Eustace
Session: Poster Display session 3
Resources:
Abstract
832 - Monospecific antibody targeting of CDH11 inhibits epithelial-to-mesenchymal transition and represses cancer stem cell-like phenotype by up-regulating miR-335 in metastatic breast cancer, in vitro and in vivo.
Presenter: Jia-Hong Chen
Session: Poster Display session 3
Resources:
Abstract
3781 - Pharmacological screening with Chk1 inhibitors identify synergistic agents to overcome resistance to platinums in basal breast and ovarian cancer
Presenter: Ana Lucia Sanabria
Session: Poster Display session 3
Resources:
Abstract
3275 - Comparison of 11 circulating miRNAs and CA125 kinetics in ovarian cancer during first line treatment: data from the randomized CHIVA trial (a GINECO-GCIG study)
Presenter: Patrick Robelin
Session: Poster Display session 3
Resources:
Abstract
3391 - Inhibiting Ehmt2 and Ezh2 histone methyltransferases alters the immune microenvironment in a Trp53-/- murine ovarian cancer model
Presenter: Pavlina Spiliopoulou
Session: Poster Display session 3
Resources:
Abstract
3839 - Fenofibrate impairs pro-tumorigenic potential of cancer stem cell-like cells within drug-resistant prostate cancer cell populations.
Presenter: Tomasz Wróbel
Session: Poster Display session 3
Resources:
Abstract