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.
Prostate cancer and prostatic diseases. 2020 Apr 20 [Epub ahead of print]
Alberto Martini, John Pfail, Francesco Montorsi, Matthew D Galsky, William K Oh
Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. ., Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Department of Urology, Vita-Salute San Raffaele University, Milan, Italy., Department of Medicine, Division of Hematology and Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
PubMed http://www.ncbi.nlm.nih.gov/pubmed/32313142