1831P - Dissecting the meaning of obesity in metastatic castration resistant prostate cancer: Size or metabolism?

Background

Obesity is associated with longer survival in patients with metastatic castration resistant prostate cancer (mCRPC). Our group has also established that elevated circulating sphingolipids are associated with a poorer prognosis in patients with mCRPC. Additionally, we have validated a CLIA-compliant circulating lipid biomarker, PCPro, which identifies patients with the poor prognostic lipid profile. This study aimed to define the metabolic characteristics underlying the obesity phenotype in mCRPC.

Methods

Six Australian Centres enrolled 72 patients with mCRPC (45% taxanes, 55% abiraterone or enzalutamide). DEXA scans assessed the distribution of lean muscle, fat, water and bone in the body. The PCPro biomarker status at baseline was assessed by mass spectrometry. Cox proportional hazards modelling assessed the association between DEXA parameters, PCPro and overall survival (OS).

Results

According to standard Body Mass Index (BMI) criteria, 32% of patients were obese, 38% overweight and 30% healthy weight range. Increasing BMI was associated with longer OS (HR=0.92, 95% CI=0.85-0.99, p=0.027). Increasing total weight (p=0.019), fat weight (p=0.014) and fat mass index (p=0.021) were all associated with improved OS. Changes in lean weight, android/gynoid weight patterns and visceral fat distribution were unrelated to OS (p>0.1). PCPro positive patients (21%, 14/66) had a shorter OS (HR=3.17, 95% CI=1.50-6.70, p=0.001). PCPro expression was an independent prognostic variable when modelled against BMI, fat weight or fat mass index.

Conclusions

Obesity and a higher amount of body fat are associated with longer OS in mCRPC. However, a PCPro positive plasma lipid profile is associated with shorter OS after adjusting for these variables. This supports the concept that clinical outcomes are driven by metabolic aspects, rather than BMI or measures of body fat alone. Future therapeutic interventions should target lipid metabolic aberrations.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Astellas, Cancer Institute New South Wales, Twin Towns, National Health and Medical Research Council of Australia.

Disclosure

L.G. Horvath: Financial Interests, Personal, Advisory Board, Honorarium donated back to Chris O'Brien Lifehouse (My hospital): Imagion Biosystems; Financial Interests, Institutional, Invited Speaker: Astellas, Janssen, Amgen; Financial Interests, Institutional, Advisory Board: Astellas, Bayer; Financial Interests, Personal, Member of Board of Directors, No payment: ANZUP (Australia and New Zealand Urogenital and Prostate) Clinical Trials Group; Financial Interests, Personal, Stocks/Shares, Stock options: Imagion Biosystems; Financial Interests, Personal, Stocks/Shares: My Emergency Doctor; Financial Interests, Institutional, Research Grant: Astellas; Financial Interests, Institutional, Invited Speaker, MK7684-001MK3475-991: MSD; Financial Interests, Institutional, Invited Speaker, AMG160 Phase 1AMG509 Phase 1AMG757 Phase 1: Amgen; Financial Interests, Institutional, Invited Speaker, 9785-CL-0335 (ARCHES): Astellas; Financial Interests, Institutional, Invited Speaker, SHR3680-002: Jiangsu Hengrui Medicines; Financial Interests, Institutional, Invited Speaker, TALAPRO2, TALAPRO3: Pfizer; Financial Interests, Institutional, Invited Speaker, CYCLONE-2, CYCLONE-3: Eli Lilly; Financial Interests, Institutional, Invited Speaker, ENZAMET, ENZARAD, DASL-HiCAP, GUIDE, ANZAdapt: ANZUP; Financial Interests, Institutional, Invited Speaker, GALAHADACISPrevalence: Janssen Cilag; Financial Interests, Institutional, Invited Speaker, GSK204697: GSK; Financial Interests, Institutional, Invited Speaker, XL184-021: Exelexis; Financial Interests, Institutional, Invited Speaker, BGB-A317BGB-283BGB-A317-290: BeiGene; Financial Interests, Institutional, Invited Speaker, FPT155-001: Five Prime; Financial Interests, Institutional, Invited Speaker, AB928CSP0003: ARCUS; Financial Interests, Institutional, Invited Speaker, ATG-017 and ATG-019: Antagene; Financial Interests, Institutional, Invited Speaker, JANUX007: Janux; Financial Interests, Institutional, Invited Speaker, Petranha: AstraZeneca; Financial Interests, Institutional, Invited Speaker, ENZAMET, ENZA-P, Upfront PSMA, ANZAdapt, GUIDE: ANZUP; Financial Interests, Institutional, Invited Speaker, HP-518-CS-001: Hinova. A.A. Azad: Financial Interests, Personal, Advisory Board: Astellas, Novartis, Sanofi, AstraZeneca, Tolmar, Telix, Merck Serono, Janssen, BMS, Ipsen, Bayer, Pfizer, Amgen, Noxopharm, Merck Sharpe Dohme; Financial Interests, Personal, Other, Consultant: Aculeus Therapeutics; Financial Interests, Personal, Invited Speaker: Astellas, Janssen, Novartis, Amgen, Ipsen, BMS, Merck Serono, Bayer, Astellas, Pfizer, Exelixis; Financial Interests, Personal, Other, Travel + Accommodation: Astellas, Merck Serono, Amgen, Novartis, Janssen, Tolmar, Pfizer, Bayer; Financial Interests, Personal, Research Grant: Astellas, Merck Serono, AstraZeneca; Financial Interests, Institutional, Invited Speaker: BMS, Bayer, AstraZeneca, Hinova, Aptevo Therapeutics, AstraZeneca, GSK, Pfizer, Astellas, SYNthorx, Bionomics, Sanofi, Ipsen, Exelixis, Merck Sharpe Dohme, Janssen, Eli Lilly, Gilead Sciences, Merck Serono, Hinova; Non-Financial Interests, Leadership Role, Chair, Translational Research Committee: ANZUP Cancer Trials Group; Non-Financial Interests, Leadership Role, Member, Scientific Advisory Committee: ANZUP Cancer Trials Group; Non-Financial Interests, Leadership Role, Chair, Urologic Oncology Committee: Clinical Oncology Society of Australia; Non-Financial Interests, Other, Editorial Board Member: BMC Urology; Non-Financial Interests, Other, Associate Editor: Cancer Research Communications, Frontiers in Oncology. A.M. Joshua: Financial Interests, Personal, Stocks/Shares: Pricillium Therapeutics; Financial Interests, Institutional, Invited Speaker: Neolukin, Janssen, Ipsen, AstraZeneca, Sanofi, Noxopharm, Iqvia, Pfizer, Novartis, BMS, Merck Serono, Eisai; Non-Financial Interests, Advisory Role: BMS, Janssen, Merck, Mayne, Roche, Bayer, Macrogenics, Pfizer, AstraZeneca, Corvus, Eli Lilly. M.R. Stockler: Financial Interests, Institutional, Research Grant, DASL: Bayer; Financial Interests, Institutional, Research Grant, Enzamet & Enzarad: Astellas; Financial Interests, Institutional, Research Grant, KEYPAD: Amgen, MSD; Financial Interests, Institutional, Research Grant, NIVORAD: BMS; Financial Interests, Institutional, Research Grant: Pfizer, Roche; Financial Interests, Institutional, Research Grant, ADELE: BeiGene; Financial Interests, Institutional, Research Grant, PARAGON2: Novartis; Financial Interests, Institutional, Other, Study Drug for Cannabis CINV Trial: Tilray. K. Samaras: Non-Financial Interests, Institutional, Invited Speaker: Endocrine Society of Australia; Financial Interests, Institutional, Research Grant: NHMRC; Other, Institutional, Member: Endocrine Society of Australia, Australian Diabetes Society; Financial Interests, Institutional, Other: Frontiers in Endocrinology (Obesity). All other authors have declared no conflicts of interest.