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
3264 - A novel preclinical model of RAF-independent MEK1 mutant tumors and its treatment with novel ATP competitive MEK inhibitor
Presenter: Luca Hegedus
Session: Poster Display session 3
Resources:
Abstract
4918 - HER2 inhibition in Aggressive Squamous Cell Carcinomas driven by a common MET Sema Domain Polymorphism
Presenter: Nur Afiqah Mohamed Salleh
Session: Poster Display session 3
Resources:
Abstract
2426 - ADAM9 as a target for lung cancer treatment
Presenter: Yuh-pyng Sher
Session: Poster Display session 3
Resources:
Abstract
5537 - Novel polyurea/polyurethane nanocapsules loaded with a tambjamine analog to improve cancer chemotherapy delivery and safety in lung cancer
Presenter: Marta Perez Hernandez
Session: Poster Display session 3
Resources:
Abstract
1597 - Discovery of Clinical Candidate DBPR112, a Furanopyrimidine-based Epidermal Growth Factor Receptor Inhibitor for the Treatment of Non-Small Cell Lung Cancer
Presenter: Hsing-pang Hsieh
Session: Poster Display session 3
Resources:
Abstract
3543 - Molecular characteristics in lung squamous cell carcinomas dependent on TP53 status – putative targets
Presenter: Vilde Haakensen
Session: Poster Display session 3
Resources:
Abstract
4111 - Comparison of molecular profiles between primary tumour and matched metastasis in non-small cell lung cancer
Presenter: Asuka Kawachi
Session: Poster Display session 3
Resources:
Abstract
4559 - Treatment with BLU-667, a potent and selective RET inhibitor, provides rapid clearance of ctDNA in Patients with RET-altered Non-Small Cell Lung Cancer (NSCLC) and Thyroid Cancer
Presenter: Giuseppe Curigliano
Session: Poster Display session 3
Resources:
Abstract
2501 - Triple MET/SRC/PIM inhibition in MET addicted tumors
Presenter: Ilaria Attili
Session: Poster Display session 3
Resources:
Abstract
5655 - Bioactivation of napabucasin triggers reactive oxygen species–mediated cancer cell death
Presenter: Fieke Froeling
Session: Poster Display session 3
Resources:
Abstract