621P - The systemic proteome of consensus molecular subtypes from patients with RAS wild-type metastatic colorectal cancer: Analysis from the randomized phase II PanaMa (AIO KRK0212) trial

Background

Consensus molecular subtypes (CMSs) are used to classify metastatic colorectal cancer (mCRC) based on gene expression patterns and may provide insights into the biology of the disease and guide treatment decisions. Here, we describe the systemic proteome of CMSs from patients with RAS wild-type (wt) mCRC receiving fluorouracil and folinic acid with or without panitumumab (Pmab) after Pmab + mFOLFOX6 induction within the randomized phase II PanaMa trial.

Methods

Serum samples were collected at baseline (prior to first cycle of chemotherapy) from 271 RAS wt mCRC patients within the PanaMa trial, and the CMS classification was determined by RNA sequencing of the primary tumor. The systemic proteome was analyzed from serum using liquid chromatography-mass spectrometry. Differential protein abundance analysis was performed to identify potential biomarkers and pathways associated with CMSs.

Results

A total of 6 differentially abundant proteins (DAPs) were identified among CMS subtypes. For CMS1, no significant DAPs were detected. CMS2 showed significant downregulation of C-reactive protein (CRP, 1.47-fold decrease; P=0.011). CMS3 showed significant upregulation of immunoglobulin-related proteins. In contrast to CMS2, CMS4 presented significant downregulation of peptidoglycan recognition protein 2 (PGLYRP2, 0.72-fold decrease; P=0.027) and upregulation of CRP (1.46-fold increase; P=0.027) and SERPINA1 (0.65-fold increase; P=0.048) and SERPINA3 (0.66-fold increase; P=0.048).

Conclusions

The identification of CMS-specific proteomic signatures helps elucidate the systemic setting of CMS-based tumor classification and ultimately may help inform the development of personalized treatment strategies for patients with mCRC.

Clinical trial identification

NCT01991873.

Editorial acknowledgement

Legal entity responsible for the study

AIO-Studien-gGmbH.

Funding

The legal funder (sponsor) of the trial was the AIO Studien gGmbH, Berlin, Germany. Amgen Inc (Thousand Oaks, CA, USA) supported the trial with study medication and a research grant to the AIO Studien gGmbH.

Disclosure

A. Ballhausen: Financial Interests, Personal, Stocks or ownership: BioNTech SE; Financial Interests, Personal, Training: Amgen; Financial Interests, Institutional, Research Grant: Amgen. A. Stahler: Financial Interests, Personal, Funding: Roche, Servier, Taiho Pharmaceutical; Financial Interests, Personal, Advisory Role: Bristol Myers Squibb/Pfizer, Novocure; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Amgen, Roche, Lilly, Pfizer. M. Karthaus: Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Amgen; Financial Interests, Personal, Advisory Role: Amgen. U. Graeven: Financial Interests, Personal, Stocks/Shares: BioNTech SE; Financial Interests, Personal, Other, Honoraria: Boehringer Ingelheim, Amgen, AstraZeneca, Bristol Myers Squibb, MSD Oncology, Sanofi Aventis GmbH, Fujifilm, Novartis, Celltrion; Financial Interests, Personal, Advisory Role: Amgen, MSD Oncology; Financial Interests, Institutional, Research Funding: Ipsen, MacroGenics; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Boehringer Ingelheim, GSK. A.H.S. Alig: Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Merck, Bristol Myers Squibb GmbH & Co. KG; Financial Interests, Personal, Other, Honoraria: MSD. E. Goekkurt: Financial Interests, Personal, Advisory Role: MSD, Bristol Myers Squibb, AstraZeneca/Daiichi Sankyo, Pfizer. A. Kurreck: Financial Interests, Personal, Other, Honoraria: Taiho Pharmaceutical, Amgen, Servier; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Medac, Amgen, Servier. S. Kasper-Virchow: Financial Interests, Personal, Other, Honoraria: Bristol Myers Squibb, MSD Oncology, AstraZeneca, Merck Serono, Amgen, Roche, Servier, Amgen, Lilly, Sanofi/Aventis, Novartis, Pierre Fabre; Financial Interests, Personal, Advisory Role: Roche, Merck Serono, Amgen, MSD Oncology, Sanofi, Bristol Myers Squibb, Lilly, Servier, AstraZeneca, Janssen-Cilag, Novartis, Pierre Fabre, Incyte; Financial Interests, Personal, Research Funding: Merck Serono, Bristol Myers Squibb, Celgene, Lilly, Servier, Roche/Genentech; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Merck Serono, Lilly, Amgen, Sanofi, Roche, Pierre Fabre, Bristol Myers Squibb. V. Heinemann: Financial Interests, Personal, Advisory Board, Honoraria: Roche, Amgen, Sanofi, Merck, Servier, Pfizer, Pierre Fabre, AstraZeneca, MSD, Seagen; Financial Interests, Personal, Advisory Role: Merck, Amgen, Roche, MSD, Bristol Myers Squibb, MSD Oncology, Novartis, Pierre Fabre, TERUMO, GSK, Servier/Pfizer, AstraZeneca, OncoSil, Nordic Bioscience; Financial Interests, Institutional, Research Funding: Merck, Amgen, Roche; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Merck. S. Stintzing: Financial Interests, Personal, Advisory Board: Amgen, Bayer, Lilly, Pierre Fabre, Merck KgaA, MSD, Roche, Sanofi, Taiho, Takeda; Financial Interests, Personal, Invited Speaker: Leo Pharma, AstraZeneca; Financial Interests, Institutional, Research Grant: Merck KGaA, Pierre Fabre, Roche. T. Trarbach: Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Ipsen, Takeda, OMT, AbbVie, Novartis, MSD, Sanofi/Aventis, Amgen, Johnson & Johnson/Janssen; Financial Interests, Personal, Research Funding: Amgen. D.P. Modest: Financial Interests, Personal, Invited Speaker: Amgen, Servier, Merck, Onkowissen, MSD, Bristol Myers Squibb, AstraZeneca, Pierre Fabre, Lilly, Cureteq, GSK, Seagen, Medison, COR2ED, JE, 21up; Financial Interests, Personal, Advisory Board: Amgen, Servier, Merck, MSD, Bristol Myers Squibb, Incyte, Takeda, G1, Onkowissen, Pierre Fabre, AstraZeneca; Financial Interests, Institutional, Research Grant: Amgen; Financial Interests, Institutional, Coordinating PI: Servier. All other authors have declared no conflicts of interest.