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
3186 - The landscape of immuno-oncology clinical trials in China
Presenter: Dawei Wu
Session: Poster Display session 3
Resources:
Abstract
3468 - Clinical Significance of Immune-related Creatine Phosphokinase Increase Associated with Anti PD1/PD-L1 immunotherapies.
Presenter: Samia Hajem
Session: Poster Display session 3
Resources:
Abstract
3836 - Thyroid toxicity and anti-thyroid antibodies as predictive markers for patients treated with anti-PD1 checkpoint therapy
Presenter: Wim Meer
Session: Poster Display session 3
Resources:
Abstract
1343 - Treatment-related adverse events and tolerability in patients with advanced renal cell carcinoma treated with first-line combination therapy with checkpoint inhibitors
Presenter: Thura Win Htut
Session: Poster Display session 3
Resources:
Abstract
5783 - Immune-related adverse events (irAEs) with single-agent PD-1 vs PD-L1 inhibitors: a meta-analysis of 8,730 patients from clinical trials
Presenter: Guru Sonpavde
Session: Poster Display session 3
Resources:
Abstract
5422 - EULAR recommendations for the diagnosis and the management of rheumatic immune-related adverse events due to cancer immunotherapy
Presenter: Marie Kostine
Session: Poster Display session 3
Resources:
Abstract
1202 - Radiographic characteristics and poor prognostic factors of interstitial lung disease (ILD) in nivolumab-treated patients with non-small cell lung cancer (NSCLC)
Presenter: Shinichi Sasaki
Session: Poster Display session 3
Resources:
Abstract
2749 - Use of Checkpoint Inhibitors (CPI) in Allogeneic Stem Cell Transplant Recipients: An Institutional Experience and A Systemic Review of the Literature
Presenter: Chantal Saberian
Session: Poster Display session 3
Resources:
Abstract
3256 - Deep Learning Radiomics distinguishes intrapulmonary Disease from Metastases in Immunotherapy-treated Melanoma Patients
Presenter: Thi Dan Linh Nguyen-Kim
Session: Poster Display session 3
Resources:
Abstract
5031 - Sarcoidosis-Like Reaction Mimics Progression in patients treated with immune checkpoint inhibitors
Presenter: Sophie Hans
Session: Poster Display session 3
Resources:
Abstract