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
3489 - Overall Survival (OS) and Metastasis-Free Survival (MFS) in men with Biochemically Relapsed (BCR) Prostate Cancer after radical prostatectomy (RP) managed with deferred Androgen Deprivation Treatment (ADT): A combined Johns Hopkins and CPDR study
Presenter: Catherine Marshall
Session: Poster Display session 3
Resources:
Abstract
4606 - ARCHES – the role of androgen deprivation therapy (ADT) with enzalutamide (ENZA) or placebo (PBO) in metastatic hormone-sensitive prostate cancer (mHSPC): Post hoc analyses of high and low disease volume and risk groups
Presenter: Arnulf Stenzl
Session: Poster Display session 3
Resources:
Abstract
2975 - Updated survival analyses of a multicentric phase II randomized trial of docetaxel (D) plus enzalutamide (E) versus docetaxel (D) as first line chemotherapy for patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) (CHEIRON study).
Presenter: Orazio Caffo
Session: Poster Display session 3
Resources:
Abstract
2708 - Real-world analysis of patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) receiving vs not receiving chemotherapy in the treatment sequence
Presenter: Alicia Morgans
Session: Poster Display session 3
Resources:
Abstract
2134 - Baseline fracture risk in men with prostate cancer starting the STAMPEDE trial
Presenter: Janet Brown
Session: Poster Display session 3
Resources:
Abstract
3504 - Risk of falls and fractures in patients with castration resistant prostate cancer (CRPC) treated with new hormonal agents – a meta-analysis of randomized controlled trials.
Presenter: Rodrigo Coutinho Mariano
Session: Poster Display session 3
Resources:
Abstract
2342 - Pain progression at initiation of chemotherapy in metastatic Castration-Resistant Prostate Cancer (mCRPC) is associated with a poor prognosis: a post-hoc analysis of FIRSTANA
Presenter: Nicolas Delanoy
Session: Poster Display session 3
Resources:
Abstract
5331 - Pain evaluation in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) treated with radium-223 (Ra-223) in the PARABO observation study
Presenter: Holger Palmedo
Session: Poster Display session 3
Resources:
Abstract
2823 - Time to castration resistant prostate cancer (CRPC) and the risk of developing immune disorders
Presenter: Vincenza Conteduca
Session: Poster Display session 3
Resources:
Abstract
1500 - Retrospective evaluation of neutropenic admission events in metastatic or high-risk hormone-sensitive prostate cancer (HSPC) patients having docetaxel chemotherapy upfront or for castrate-resistant prostate cancer (CRPC) in STAMPEDE
Presenter: Harriet Mintz
Session: Poster Display session 3
Resources:
Abstract