The proportion of patients with breast cancer (BC) who are overweight or obese has been increasing. Obesity is associated with worse prognosis and with differential response to several anti-cancer therapies. However, we still lack knowledge about potential differential efficacy of most drugs according to BMI. Here, we aimed to investigate how BMI is documented in recent clinical drug trials (CTs), in trials investigating gene expression profiles (GEPs) and molecular screening programs (MS).
A search of Pubmed and ClinicalTrials.gov was performed using medical subject heading terms and words related to the treatments (CDK4/6 inhibitors, antibody drug conjugates, oral selective estrogen receptor degrader, PARP inhibitors, tyrosine kinase inhibitors, mTOR inhibitors, immune checkpoint inhibitors, PIK3CA inhibitors and others). The considered GEPs were: OncotypeDx, Mammaprint, EPClin, Prosigna, BreastCancerIndex, and OncoMasTR. Only phase III and IV CTs with a full manuscript available on 15/01/2023 were included. Documentation of BMI category was assessed and if reported, it was checked if subgroup analyses were performed. We also searched for other measures of adiposity.
In total, 80 CTs were included. Of the 23 evaluated drugs, 19 (82.6%) are given as a fixed dose independent of patient weight. Maximum or minimum BMI was not an exclusion criterium in any of the CTs. Distribution of patients according to BMI was mentioned in the original manuscript of one CT. Initially, this was also the only trial were a subgroup analysis was performed. No other measures of adiposity were mentioned in any of the CTs. Additional retrospective analyses on the impact of BMI were performed in 5 CTs. The initial manuscript of all GEPs and MS was lacking information regarding patient’s BMI but was retrospectively evaluated for 3/6 (50%) GEPs.
This study emphasizes that most drugs are given at fixed dose and the gap in knowledge we have on the efficacy of the novel anti-cancer treatments and the use of GEP and MS according to patient adiposity. As the prevalence of obesity is increasing worldwide, the evaluation of body composition is needed to increase knowledge on optimal use of drugs in clinical practice.
The authors.
Has not received any funding.
K. Punie: Financial Interests, Institutional, Advisory Board: AstraZeneca, Novartis, Roche, Vifor Pharma, Eli Lilly, Pierre Fabre, McCann Health, Roularta, Teva, Gilead Sciences, Pfizer, Gilead, MSD; Financial Interests, Institutional, Invited Speaker: Pfizer, Roche, Novartis, Eli Lilly, Mundi Pharma, MSD, Medscape, MSD; Financial Interests, Institutional, Other, Consultancy: Roche; Financial Interests, Personal, Other, Consultancy: Gilead, Novartis, MSD, Roche; Financial Interests, Personal, Advisory Board: Seagen; Financial Interests, Personal, Invited Speaker: Sanofi, AstraZeneca; Financial Interests, Institutional, Funding: Sanofi; Non-Financial Interests, Principal Investigator: EORTC 1745-ETF-BCG trial; Non-Financial Interests, Other, Committee member: ESMO Young Oncologists Committee; Non-Financial Interests, Invited Speaker: BSMO; Non-Financial Interests, Other, Committee Member: ESMO Resilience Task Force; Non-Financial Interests, Advisory Role: Commission personalized medecine Federal Government Belgium; Non-Financial Interests, Advisory Role, External Scientific Advisor: European Medicine Agency. H. Wildiers: Financial Interests, Institutional, Advisory Board: Roche, Lilly, AstraZeneca, Daiichi Sankyo, PSI Cro AG, KCE, MSD, MSD, E Squared Communications LLC; Financial Interests, Institutional, Invited Speaker: Eisai, AstraZeneca; Financial Interests, Institutional, Other, Consultancy fee: AbbVie, Immutep Pty; Financial Interests, Institutional, Expert Testimony: Daiichi Sankyo; Financial Interests, Institutional, Other, Consultancy: Daiichi Sankyo; Financial Interests, Institutional, Research Grant, Grant to the Leuven Breast Center to support the research database: Roche; Financial Interests, Institutional, Research Grant, Grant to institute to perform a multicentric national academic trial: Novartis; Other, Travel & accomodations: Pfizer; Other, Travel & accomodation: Roche; Other, Subscription fee: Gilead. All other authors have declared no conflicts of interest.