Abstract 683P
Background
MFS (metastases or death) is a surrogate for overall survival (OS) in men with non-metastatic CRPC, however this endpoint may take years to develop in men with non-metastatic castrate-sensitive disease. Other evidence-based intermediates that occur earlier in the disease course are needed for clinical trial design to expedite evaluating new therapies. We examined whether CRPC-FS (CRPC or death) is a reasonable intermediate endpoint for MFS in patients with biochemical recurrence (BCR) after radical prostatectomy (RP).
Methods
This was a retrospective cohort study (1988-2017) of men with BCR after RP who had PSA doubling time <9 months and no evidence of metastasis at the time of starting ADT (n=210) at 8 Veterans Affairs Hospitals. The primary outcome was the correlation between CRPC-FS and MFS. Secondary outcomes were time to metastasis and time to CRPC. Kendall’s Tau was used to test the correlation between CRPC-FS and MFS and between time to CRPC and time to metastasis. Multivariable Cox models were fit to examine clinicopathologic features linked with the primary and secondary outcomes.
Results
Median MFS was 104 months (95% CI 83-114) and 100 months (95% CI 80-114) for CRPC-FS. Kendall’s Tau for the correlation between CRPC-FS and MFS and between time to CRPC and time to metastasis was 0.867 (95% CI 0.765-0.968) and 0.764 (95% CI 0.644-0.884), respectively, indicating strong correlations between CRPC and metastasis-related outcomes. N+ disease and higher PSA at start of ADT were linked with shorter CRPC-FS or MFS with similar hazard ratios for both outcomes (all p≤0.003). Black race was also linked with a qualitatively similar lower risk of CRPS-FS (HR 0.56, 95% CI 0.33-0.96) and MFS (HR 0.63, 95% CI 0.37-1.08) vs. white race.
Conclusions
In men with BCR after RP and no metastasis at the time of ADT start, CRPC-FS and MFS were highly correlated and the predictors of the two outcomes were similar. These results may have important clinical trial ramifications, including using CRPC-FS as an intermediate endpoint in trials for men with BCR after local therapy.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Pfizer Inc. and Astellas Pharma, Inc.
Funding
Pfizer Inc. and Astellas Pharma, Inc.
Disclosure
S.J. Freedland: Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer Inc.; Travel/Accommodation/Expenses: Astellas; Travel/Accommodation/Expenses: Janssen; Travel/Accommodation/Expenses: Bayer; Travel/Accommodation/Expenses: Myovant; Travel/Accommodation/Expenses: AstraZeneca; Travel/Accommodation/Expenses: Merck; Travel/Accommodation/Expenses: Dendreon; Travel/Accommodation/Expenses: Sanofi. C.J.D. Wallis: Advisory/Consultancy: Janssen Canada. A. De Hoedt: Research grant/Funding (institution): Pfizer Inc.; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Sanofi; Research grant/Funding (institution): Janssen; Research grant/Funding (institution): Blue Earth Diagnostics; Research grant/Funding (institution): Ferring; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Myriad; Research grant/Funding (institution): Lung Life AI; Research grant/Funding (institution): OncoCell MDx; Research grant/Funding (institution): Dendreon. All other authors have declared no conflicts of interest.