Surrogate endpoints for overall survival for patients with metastatic hormone-sensitive prostate cancer in the...

Metastasis-free survival has been shown to be a robust surrogate for overall survival (OS) in men with nonmetastatic prostate cancer (PC). However, this surrogate only holds true for a select subset of patients, and leaves those trials analyzing metastatic disease at a disadvantage. We aimed to identify the best surrogate for predicting OS in patients with metastatic hormone-sensitive PC.

We analyzed data from the Chemohormonal Therapy versus Androgen Ablation Randomized Trial for Extensive Disease trial in which patients were randomly assigned to receive either androgen deprivation therapy (ADT) or ADT plus docetaxel. PSA response, progression and development of castration-resistant PC (CRPC) within 6 and 12 months were investigated as potential OS surrogates, in accordance with the Prentice Criteria. The proportion the of treatment effect (PTE) was calculated for each surrogate and used to identify the best one.

Data from 790 patients were considered: 393 (49.7%) men received ADT alone, while 397 (50.3%) received combination therapy. Four intermediate clinical endpoints met the criteria for surrogacy: progression within 6 months (HR: 5.70; 95%CI: 4.26, 7.64; p < 0.001) and 12 months (HR: 7.09; 95%CI: 5.16, 9.76; p < 0.001) as well as development of CRPC within 6 (HR: 5.11; 95%CI: 3.81, 6.85; p < 0.001) and 12 months (HR: 6.24; 95%CI: 4.58, 8.51; p < 0.001). The PTE for the four surrogates were 88%, 52%, 80%, and 46%, respectively. The 2-year OS rates for patients who progressed within 6 months of randomization were 42 versus 89% for the patient population that did not progress that quickly.

Progression within 6 months following combination therapy emerged as the best surrogate for OS.