1615P - A new prognostic model of overall survival (OS) in patients (pts) with metastatic hormone sensitive prostate cancer (mHSPC)

Background

Limited research has explored the prognostic factors in patients with mHSPC. Previous findings have shown that disease volume and metastatic diagnosis status are important prognostic factors for OS. We sought to develop and validate a prognostic model of OS in pts with mHSPC.

Methods

Data from 4 randomized phase III trials comparing treatment regimens (standard of care (SOC) vs SOC plus docetaxel) were utilized. OS was defined as time between date of randomization to date of death/or last follow-up. Variables with a missing rate less than 50% in at least one of the four trials were considered, including age, ECOG performance status (PS), radical prostatectomy, prior radiation therapy, Gleason score, site of metastases, number of bone metastases, opioid analgesic use, disease volume, M1 metastatic diagnosis, hemoglobin, albumin, PSA, and alkaline phosphatase. Multiple imputation was employed to handle missing values. We utilized two randomized trials (CHAARTED and GETUG-15) for developing the model. Additionally, we employed an ensemble proportional hazards model where the final model was constructed based on the augmented training set incorporating two risk scores from trial-specific models. We validated the fitted model using two comparisons from the STAMPEDE trial (SOC vs. SOC + docetaxel (A vs C) and SOC vs. SOC + zoledronic acid+ docetaxel (A vs E)). Model discrimination was assessed using the time-dependent area under the receiver operating characteristic curve (tAUC).

Results

This analysis included 2627 pts (1585 deaths) with median follow-up time of 60.3 months. Median age is 69 years, 72% of pts had ECOG PS of 0, 85% had de-novo metastases and 51% had high disease volume. Important prognostic factors of OS were disease volume, PS, radical prostatectomy, alkaline phosphatase and hemoglobin. The tAUCs in the two STAMPEDE testing sets and in the model with only the controls were 0.73 (95% CI, 0.71-0.77), 0.71 (95%CI, 0.67-0.74) and 0.73 (95%CI, 0.69-0.77), respectively.

Conclusions

The model identified novel prognostic factors of OS in men with mHSPC. It offers the potential for classifying pts into risk groups useful in selecting men in future mHSPC trials. Further validation of this prognostic model of OS is warranted.

Clinical trial identification

Data from four phase III trials are included in this analysis. GETUG 15 (NCT00104715), STAMPEDE (NCT00268476) and CHAARTED (NCT00309985).

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Prostate Cancer Foundation Challenge Award, Prostate Cancer UK Research Innovation Award RIA16-ST2-020, National Institutes of Health Grants R01 CA256157 and R01 CA249279, the UKRI Medical Research Council Grant number: MC_UU_00004/06 and the United States Army Medical Research Award HT9425-23-1-0393.

Disclosure

S. Halabi: Financial Interests, Personal, Other, Member of DSMB: Sanofi, Aveo Oncology, BMS, Janssen, CG Oncology; Financial Interests, Institutional, Funding: ASCO; Financial Interests, Institutional, Coordinating PI, co-PI on Funded Research: Astellas. M.K. Parmar: Financial Interests, Institutional, Full or part-time Employment, Director at MRC Clinical Trials Unit at UCL: Medical Research Council Clinical Trials Unit at UCL; Financial Interests, Personal and Institutional, Research Grant: AstraZeneca, Astellas, Janssen, Baxter, GSK; Financial Interests, Institutional, Research Grant: Clovis, Abcodia Pvt Ltd., Akagera, Amgen, Aspirin Foundation, Bayer, BMS US, Bri-BioCepheid, Cipla, CSL Behring, Eli Lilly, Emergent Biosolutions, Gilead Sciences, Grifols, Johnson & Johnson, Pfizer, Sanofi, ViiVHealthcare, Micronoma, Modus Theraputics, Mylan, Serum Institute of India, Shionogi, SyntenyBiotechnology, Takeda, Tibotec, Transgene, Virco and Xenothera; Non-Financial Interests, Advisory Role, Euro Ewing Consortium: University College London; Non-Financial Interests, Advisory Role, rEECur: University of Birmingham; Non-Financial Interests, Advisory Role, CompARE Trial: University of Birmingham; Non-Financial Interests, Advisory Role, ROSSINI Trial Platform: University of Birmingham. M.A. Carducci: Financial Interests, Personal, Advisory Board: Pfizer, Remedica, AstraZeneca; Financial Interests, Personal, Other, Data Safety Monitoring Board: Acrivon; Financial Interests, Personal, Other, JCO Editor: American Society of Clinical Oncology; Financial Interests, Institutional, Steering Committee Member: Arcus; Financial Interests, Institutional, Local PI: Celgene; Non-Financial Interests, Leadership Role: ECOG-ACRIN. G. Gravis: Financial Interests, Institutional, Invited Speaker: AAA, Amgen, Astellas, BMS, Janssen, MSD, Pfizer, Ipsen, AstraZeneca, alliance Merck Pfizer, Bayer, EISAI; Financial Interests, Institutional, Advisory Board: Alliance Merck-Pfizer, BMS, Janssen, Pfizer, Ipsen, Bayer, EISAI; Financial Interests, Institutional, Funding: Janssen; Financial Interests, Institutional, Coordinating PI: BMS; Non-Financial Interests, Principal Investigator: Ipsen, BMS, Merck. N.D. James: Financial Interests, Personal, Advisory Board, Advice around PARP inhibitors: AstraZeneca; Financial Interests, Personal, Advisory Board, Prostate cancer therapies: Janssen, Clovis, Novartis; Financial Interests, Institutional, Advisory Board, Assisted with submissions regarding licencing for abiraterone: Janssen; Financial Interests, Personal, Advisory Board, Docetaxel: Sanofi; Financial Interests, Institutional, Advisory Board, Providing STAMPEDE trial data to facilitate licence extensions internationally for docetaxel: Sanofi; Financial Interests, Personal, Advisory Board, Bladder cancer therapy: Merck; Financial Interests, Personal, Advisory Board, Advice around novel hormone therapies for prostate cancer: Bayer; Financial Interests, Personal, Invited Speaker, Lecture tour in Brazil August 2022 - speaking on therapy for advanced prostate cancer: Merck Sharp & Dohme (UK) Limited; Financial Interests, Institutional, Coordinating PI, Funding for STAMPEDE trial: Janssen, Astellas; Financial Interests, Institutional, Coordinating PI, Funding for RADIO trial bladder cancer: AstraZeneca. C. Sweeney: Financial Interests, Personal, Advisory Board, Consultancy: Genentech Roche, Bayer, Astellas, Pfizer, Pfizer, Sanofi, Lilly; Financial Interests, Personal, Other, Consultancy: Janssen, MSD; Financial Interests, Personal, Advisory Board: Point, Cellcentric; Financial Interests, Personal, Advisory Board, Consultant: Advancell; Financial Interests, Personal, Advisory Board, Advisory Boards: BMS; Financial Interests, Personal, Advisory Board, Consutlant: Amphista; Financial Interests, Personal, Stocks/Shares: Leuchemix; Financial Interests, Personal, Stocks/Shares, Consultant: Advancell; Financial Interests, Institutional, Advisory Board, Abiraterone plus cabozantinib: Exelixis; Financial Interests, Institutional, Research Grant: Bayer, Janssen, Astellas, Pfizer, Dendreon, Sanofi. All other authors have declared no conflicts of interest.