59P - Identifying blood-based proteomic mediators of cancer-associated cachexia in non-small cell lung cancer in the TRACERx study

Background

Cancer-associated cachexia (CAC) is a complex, debilitating, wasting syndrome that limits patient fitness and the effectiveness of cancer therapies, resulting in poor outcomes. It involves the loss of muscle with or without fat loss, and associated weight loss. Although several plasma proteins have been found to be associated with the development of CAC, there are currently no biomarkers that can help identify patients who are risk of developing CAC, and none that are used to guide clinical intervention.

Methods

TRACERx (NCT01888601) is a prospective observational study of patients with operable early stage (I-III) non-small cell lung cancer (NSCLC) who are followed up from surgery through to relapse or cure. In patients that do and do not develop CAC, blood samples taken at diagnosis (n=678), at first relapse (n=184), and after follow up without relapse (n=212) were subjected to the Olink Explore 3072 proteomics platform to measure the expression of approximately 3000 proteins. Body composition measurements were defined as area (cm²) at the third lumbar vertebra level from routine CT images analysed with the Voronoi Health Analytics Data Analysis Facilitation Suite, an automated deep learning-based pipeline.

Results

In a smaller cohort of patients before surgery we previously showed differential protein expression in the blood proteome at relapse in patients who did and did not develop CAC, with no significant differences before surgery (Al-Sawaf et al., 2023). Here we present an extended cohort of patients with longitudinal blood samples and repeat analysis of differential protein expression between CAC and non-CAC patients. We further consider the association of protein expression with CAC after adjusting for confounding factors.

Conclusions

There are proteins that are differentially expressed in the blood plasma proteome in NSCLC patients that develop CAC, compared to those that do not. These proteins may be candidates for non-invasive biomarkers for the early detection of CAC, which could allow for early intervention and treatment stratification.

Editorial acknowledgement

Clinical trial identification

NCT01888601.

Legal entity responsible for the study

University College London.

Funding

Cancer Grand Challenges CANCAN, Cancer Research UK.

Disclosure

C. Swanton: Financial Interests, Personal, Invited Speaker, Activity took place in 2016: Pfizer, Celgene; Financial Interests, Personal, Invited Speaker, October 26th 2020: Novartis; Financial Interests, Personal, Invited Speaker: Roche/Ventana, BMS, AstraZeneca, MSD, Illumina, GSK; Financial Interests, Personal, Advisory Board, Ad Board - November 12th, 2020: Amgen; Financial Interests, Personal, Advisory Board, Current - since 2018: Genentech; Financial Interests, Personal, Advisory Board: Sarah Canon Research Institute; Financial Interests, Personal, Advisory Board, Joined October 2020. Also have stock options: Bicycle Therapeutics; Financial Interests, Personal, Other, Consultancy: Medicxi; Financial Interests, Personal, Advisory Board, Member of the Science Advisory Board. Also had stock options until June 2021: GRAIL; Financial Interests, Personal, Other, Consultancy agreement: Roche Innovation Centre Shanghai; Financial Interests, Personal, Advisory Board, 29 November - 1 December 2022: Novartis; Financial Interests, Personal, Invited Speaker, Oncology Collective - 2nd Nov - 4 Nov 2022 - Atlanta, USA: Roche; Financial Interests, Personal, Advisory Board, ctDNA advisory Board - 24th March 2023: AstraZeneca; Financial Interests, Personal, Invited Speaker, Pfizer Oncology 'Leading the revolution for the future: Pfizer; Financial Interests, Personal, Advisory Board, Scientific Advisory Board and Stock options from September 2023: Relay Therapeutics; Financial Interests, Personal, Advisory Board, Member of the Scientific Advisory Board: SAGA Diagnostics; Financial Interests, Personal, Full or part-time Employment, Chief Clinician since October 2017: Cancer Research UK; Financial Interests, Personal, Ownership Interest, Co-Founder of Achilles Therapeutics. Also, have stock options in this company: Achilles Therapeutics; Financial Interests, Personal, Stocks/Shares, Stocks owned until June 2021: GRAIL, Apogen Biotechnologies; Financial Interests, Personal, Stocks/Shares: Epic Biosciences, Bicycle Therapeutics; Financial Interests, Personal, Stocks/Shares, Stock options: Relay Therapeutics; Financial Interests, Institutional, Research Grant, Funded RUBICON grant - October 2018 - April 2021: Bristol Myers Squibb; Financial Interests, Institutional, Research Grant, Collaboration in minimal residual disease sequencing technologies: Archer Dx Inc; Financial Interests, Institutional, Research Grant: Pfizer, Boehringer Ingelheim; Financial Interests, Institutional, Invited Speaker, Chief Investigator for the MeRmaiD 1and 2 clinical trials and chair of the steering committee: AstraZeneca; Financial Interests, Institutional, Research Grant, Research grant from Oct 2019 - July 2023 - Genetics of CIN and SCNAs for Targeted Discovery (SCEPTRE): Ono Pharmaceutical; Financial Interests, Institutional, Research Grant, Research Grants from 2015: Roche; Financial Interests, Personal, Other, Co-chief investigator: NHS-Galleri Clinical Trial; Financial Interests, Institutional, Research Grant, from October 2022: Personalis; Non-Financial Interests, Personal, Principal Investigator, Chief Investigator for MeRmaiD 1and 2 clinical trials: AstraZeneca; Non-Financial Interests, Personal, Member of Board of Directors, From 2019-2022: AACR; Non-Financial Interests, Personal, Other, Board of Directors: AACR; Non-Financial Interests, Personal, Advisory Role, EACR Advisory Council member: EACR. M. Jamal-Hanjani: Financial Interests, Personal, Invited Speaker, Invited speaker honorarium: Oslo Cancer Cluster, Astex Pharmaceutical; Financial Interests, Personal, Invited Speaker, Speaker honorarium: Pfizer, Bristol Myers Squibb; Financial Interests, Personal, Advisory Board, Cancer cachexia research advisory board: Pfizer; Non-Financial Interests, Personal, Advisory Role, Scientific Advisory Board and Steering Committee member: Achilles Therapeutics; Other, Personal, Other, I am named as co-inventor on patent PCT/US2017/028013 relating to methods for lung cancer detection: Patent. All other authors have declared no conflicts of interest.