Abstract 1701P
Background
In 2015, the Colorectal Cancer (CRC) Subtyping Consortium published four gene expression consensus molecular subtypes (CMS) from early stage CRC patients: CMS1 (immune), CMS2 (canonical), CMS3 (metabolic), and CMS4 (mesenchymal). The distribution of CMS groups is not well described for late-stage CRC.
Methods
The Copenhagen Prospective Personalized Oncology study comprises patients with advanced solid cancers and exhausted treatment options referred to a phase I unit. 227 CRC patients enrolled 2017-2020 underwent metastatic biopsy and samples were classified using CMSClassifier. Samples with a subtype probability > 0.5 were assigned a single subtype, while samples with subtype probabilities > 0.2 and < 0.5 were considered mixed CMS. Subtypes were correlated to clinical characteristics.
Results
One third of patients in our study were classified as mixed CMS (Table). No samples were indeterminate. Female patients were overrepresented in CMS1 and underrepresented in CMS4. The most common primary tumor location was the right colon for patients with CMS1 and 3, left colon for patients with CMS2, while primary tumor location for patients with CMS4 varied across regions. Lactate Dehydrogenase (LDH) was higher in patients with CMS2 compared to other subtypes, whereas C-Reactive Protein (CRP) was 3-fold higher in patients with CMS1. Table: 1701P
Patient characteristics by CMS subtype
| CMS1 (6%, n=14) | CMS2 (27%, n=62) | CMS3 (7%, n=15) | CMS4 (25%, n=57) | Mixed (35%, n=79) | Total (n=227) | |
| Sex | ||||||
| Male | 6 (43 %) | 33 (53 %) | 7 (47 %) | 38 (67 %) | 47 (59 %) | 131 (58 %) |
| Female | 8 (57 %) | 29 (47 %) | 8 (53 %) | 19 (33 %) | 32 (41 %) | 96 (42 %) |
| Performance score | ||||||
| 0 | 6 (43 %) | 28 (45 %) | 7 (47 %) | 21 (37 %) | 39 (49 %) | 101 (44 %) |
| 1 | 8 (57 %) | 28 (45 %) | 8 (53 %) | 34 (60 %) | 36 (46 %) | 114 (50 %) |
| Primary tumor location | ||||||
| Right colon | 7 (50 %) | 11 (18 %) | 8 (53 %) | 20 (35 %) | 34 (43 %) | 80 (35 %) |
| Left colon | 3 (21 %) | 29 (47 %) | 2 (13 %) | 13 (23 %) | 20 (25 %) | 67 (30 %) |
| Rectum | 4 (29 %) | 21 (34 %) | 4 (27 %) | 19 (33 %) | 24 (30 %) | 72 (32 %) |
| Mean CRP - mg/L (SD) | 84 (± 110) | 32 (± 52) | 28 (± 35) | 34 (± 51) | 38 (± 54) | 38 (± 57) |
| Mean LDH - U/L (SD) | 220 (± 59) | 370 (± 230) | 280 (± 99) | 270 (± 140) | 300 (± 200) | 300 (± 190) |
Conclusions
CMS distribution in this cohort of late-stage CRC patients differs from previous published results for patients with early CRC. Notably, we found that a third of patients had mixed CMS. This may represent a transition phenotype for late-stage CRC or possibly intra-tumoral heterogeneity. Since the biopsy from the primary site was not available for this study, we could not assess intraindividual tumor heterogeneity. Our results for sex and primary tumor location across subtypes were comparable with previous findings. Consistent with expectations, we found high CRP levels in patients with CMS1 representing immune system activation.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
K.S. Rohrberg: Financial Interests, Personal, Invited Speaker: Bayer, Amgen; Financial Interests, Institutional, Invited Speaker, Compensation for conduction of clinical trial: Lilly, Roche/Genentech, Bristol Myers Squibb, Symphogen, Pfizer, Novartis, Alligator Bioscience, Genmab, BioInvent, Monta Bioscience; Financial Interests, Institutional, Other, Compensation for conduction of clinical trial: Bayer, Incyte, Puma Biotechnology, Orion Clinical. I. Spanggaard: Financial Interests, Institutional, Invited Speaker: Roche, Puma Biotechnology, MSD, Genentech, Incyte, AstraZeneca, Orion, Pfizer; Non-Financial Interests, Principal Investigator: Roche, Puma Biotechnology, MSD, Genentech, Incyte, AstraZeneca, Orion, Pfizer. M. Hoejgaard: Financial Interests, Personal, Other, Advisory role for various diagnostic companies/investors: LingoMedical; Financial Interests, Personal, Stocks/Shares, Stocks, <20000USD: Bavarian Nordic, Pacific Biosciences, Illumina Inc.; Financial Interests, Personal, Stocks/Shares, Shares<20000USD: Agilent; Non-Financial Interests, Principal Investigator, TRESR trial and MYTHIC trial: Repare Therapeutics; Non-Financial Interests, Principal Investigator, AMG160 master protocol: Amgen; Non-Financial Interests, Principal Investigator, INC93318-122: Incyte Cooperation; Other, Other, Board member, tumor agnostic board. Public service: Danish Medicines Council. C. Qvortrup: Non-Financial Interests, Personal, Advisory Board: MSD, AstraZeneca; Non-Financial Interests, Institutional, Principal Investigator: Pierre Fabre, Roche, Servier. All other authors have declared no conflicts of interest.