1635P - Validation of automated bone scan index as a progression endpoint in two phase III studies of metastatic castration resistant prostate cancer (mCRPC) patients

Background

We previously developed a bone progression criterion by measuring the change in metastatic disease burden in bone as quantified by the automated bone scan index (aBSI) and compared it to the Prostate Cancer Working Group 3 progression definition. This study sought to validate the increase in aBSI as a bone progression endpoint in two phase 3 clinical trials.

Methods

We used data from the Cougar COU302 (T1) NCT00638690 and Alliance A031201 (T2) NCT01949337 trials of mCRPC chemo naïve patients. Bone scan images were collected and analyzed for aBSI calculation from all study timepoints. Thresholds for an absolute increase in aBSI from baseline were evaluated as a metric for the time to bone progression and the endpoint bone progression-free survival (bPFS). The association between bPFS for each threshold and outcome (overall survival (OS) and radiographic progression-free survival (rPFS)) was computed with Kendall’s tau.

Results

Patients with imaging at multiple timepoints and recorded outcomes data were included; 802 and 648 patients from T1 and T2 respectively. An absolute increase in aBSI of 0.8 as a bone progression was found to have optimal event proportion and association with OS. In T1, there were 548 deaths and 516 radiographic progression events. The association between OS and bPFS was tau = 0.39. In T2, there were 449 deaths and 485 radiographic progression events. The association between OS and bPFS was tau = 0.61. Additional results are detailed in the table below. Table: 1635P

Conclusions

This study validates our previous finding that time to an absolute aBSI increase of more than 0.6 is associated with rPFS and OS. An objective measurement of total increase in bone burden of disease with aBSI can augment the current rPFS criteria in clinical trials. Future work will incorporate aBSI progression into the conventional rPFS endpoint and explore its association with OS.

Clinical trial identification

NCT00638690; NCT01949337.

Editorial acknowledgement

Legal entity responsible for the study

Memorial Sloan Kettering Cancer Center.

Funding

Foundation for the National Institutes of Health (FNIH).

Disclosure

K. Sjöstrand: Financial Interests, Institutional, Full or part-time Employment: Lantheus, Inc.; Financial Interests, Personal, Stocks/Shares: Lantheus, Inc. A. Anand: Financial Interests, Personal, Full or part-time Employment: Lantheus, Inc. G. Borzillo: Financial Interests, Institutional, Full or part-time Employment: J&J Innovative Medicine; Financial Interests, Personal, Stocks/Shares: JNJ. S. Larson: Financial Interests, Institutional, Research Grant: Y-mAbs Therapeutics, Inc., Genentech, Inc., WILEX AG, Telix Pharmaceuticals Limited, Regeneron Pharmaceuticals; Financial Interests, Personal, Stocks or ownership: Elucida Oncology, Inc; Financial Interests, Personal, Stocks/Shares: ImaginAb, Inc., Y-mAbs Therapeutics; Financial Interests, Personal, Speaker, Consultant, Advisor: Cynvec, LLC, Eli Lilly &Co., Prescient Therapeutics Limited, Advanced Innovative Partners, LLC, Gerson Lehrman Group, Progenics Pharmaceuticals, Inc., Exini,Inc, Janssen Pharmaceuticals, Medimagemetric LLC; Financial Interests, Personal, Other: Samus Therapeutics, Inc., Elucida Oncology, Inc., Y-mAbs Therapeutics, Inc., Soothsayer. M.J. Morris: Financial Interests, Personal, Advisory Board: Oric, Pfizer, Exelixis, Lantheus, AstraZeneca, Amgen, Daiichi Sankyo, Convergent, Clarity Pharmaceuticals, Blue Earth Diagnostics, POINT Biopharma, Telix, Z-alpha; Financial Interests, Personal, Invited Speaker: Progenics, ITM Isotope Technologies; Financial Interests, Personal, Stocks/Shares: Doximity; Financial Interests, Institutional, Coordinating PI: Novartis, Celgen; Financial Interests, Institutional, Local PI: Corcept, Janssen, Astellas; Non-Financial Interests, Advisory Role: Bayer, Janssen Oncology, Novartis; Other, Travel to conference: AstraZeneca; Other, Travel/lodging at conference: APCCC. All other authors have declared no conflicts of interest.