Correlation of Prostate-specific Antigen Kinetics with Overall Survival and Radiological Progression-free Survival in Metastatic Castration-sensitive Prostate Cancer Treated with Abiraterone Acetate plus Prednisone or Placebos Added to Androgen Deprivation Therapy: Post Hoc Analysis of Phase 3 LATITUDE Study.

Autor: Matsubara N; National Cancer Center Hospital East, Chiba, Japan. Electronic address: nmatsuba@east.ncc.go.jp., Chi KN; BC Cancer Agency, Vancouver, BC, Canada., Özgüroğlu M; Cerrahpaşa Medical Faculty, Istanbul University-Cerrahpasa, Istanbul, Turkey., Rodriguez-Antolin A; 12 de Octubre University Hospital, Madrid, Spain., Feyerabend S; Studienpraxis Urologie, Nürtingen, Germany., Fein L; Instituto de Oncologia de Rosário, Rosário, Argentina., Alekseev BY; P.A. Hertsen Moscow Cancer Research Institute, Moscow, Russian Federation., Sulur G; Janssen Research & Development, Los Angeles, CA, USA., Protheroe A; Oxford University Hospitals Foundation NHS Trust, Oxford, UK., Li S; Janssen Research & Development, Spring House, PA, USA., Mundle S; Janssen Research & Development, Raritan, NJ, USA., De Porre P; Janssen Research & Development, Beerse, Belgium., Tran N; Janssen Research & Development, Los Angeles, CA, USA., Fizazi K; Institut Gustave Roussy, University of Paris Sud, Villejuif, France.
Jazyk: angličtina
Zdroj: European urology [Eur Urol] 2020 Apr; Vol. 77 (4), pp. 494-500. Date of Electronic Publication: 2019 Dec 13.
DOI: 10.1016/j.eururo.2019.11.021
Abstrakt: Background: LATITUDE, a randomized, double-blind trial, compared abiraterone acetate and prednisone (AAP) + androgen deprivation therapy (ADT) versus placebo (PBO) + ADT in high-risk metastatic castration-sensitive prostate cancer (mCSPC).
Objective: To assess the correlation of prostate-specific antigen (PSA) kinetics with overall survival (OS) and radiological progression-free survival (rPFS).
Design, Setting, and Participants: A post hoc analysis of data from 597 men receiving AAP + ADT and 602 receiving PBO + ADT.
Outcome Measurements and Statistical Analysis: The associations of PSA-related outcomes (rates of confirmed 50% [PSA50] and 90% [PSA90] decline from baseline PSA [Prostate Cancer Working Group 2 criteria], rates of PSA < 0.2 ng/ml, median nadir PSA, time to PSA nadir [TPN], and time to PSA progression [TPP] with long-term outcomes [OS and rPFS]) were evaluated. Hazard ratios (HRs) were estimated using Cox proportional hazard model. Correlations of TPP with coprimary endpoints rPFS and OS were evaluated using Kendall's tau (KT).
Results and Limitations: AAP + ADT significantly delayed median TPP versus PBO + ADT (33.2 vs 7.4 mo; HR: 0.3, p <  0.001). TPP correlated with rPFS (KT = 0.921) and OS (KT = 0.666). In the AAP + ADT group, 91% had PSA50 and 79% had PSA90 responses (relative risk [RR]: 1.36 and 2.30, respectively; p <  0.001 for both comparisons vs PBO + ADT). Compared with nonresponders, PSA50 and PSA90 responders had reduced risk of death (RR: 0.44 and 0.12, respectively). At 6 mo, 40% receiving AAP + ADT and 6.5% receiving PBO + ADT achieved PSA ≤0.1 ng/ml, which was significantly associated with longer rPFS and OS. Median nadir PSA was 0.09 ng/ml with AAP + ADT versus 2.36 ng/ml with PBO + ADT. Median TPN (AAP + ADT, 6.4 mo; PBO + ADT, 3.8 mo) positively correlated with rPFS and OS.
Conclusions: Superior PSA response dynamics with AAP + ADT versus ADT + PBO strongly correlated with long-term outcomes of rPFS and OS in high-risk mCSPC.
Patient Summary: We found that low prostate-specific antigen levels (≤0.1 ng/ml) after 6 mo may indicate a good long-term response to treatment. Our results need confirmation.
(Copyright © 2019 European Association of Urology. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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