ESMO 2022: 8-Month PSA Strongly Predicts Outcomes of Men with Metastatic Castration-Sensitive Prostate Cancer in the PEACE-1 Phase 3 Trial

(UroToday.com) The 2022 ESMO annual meeting featured a prostate cancer session, including a presentation by Dr. Gwenaelle Mescam discussing 8-month PSA outcomes of men with metastatic castration-sensitive prostate cancer (mCSPC) in the PEACE-1 phase 3 trial. Previously published, the addition of abiraterone acetate plus prednisone to androgen deprivation therapy (ADT) with or without docetaxel, improved overall survival (OS) in men with de novo mCSPC in the PEACE-1 phase 3 trial.1 The 8-month PSA decline to undetectable levels has been associated with improved OS and radiological progression-free survival (rPFS) in mCSPC men treated with ADT plus docetaxel or abiraterone acetate plus prednisone. At ESMO 2022, Dr. Mescam and colleagues assessed the association of 8-month PSA value with rPFS and OS in mCSPC men treated in PEACE-1 with the triplet systemic association: ADT+ docetaxel + abiraterone acetate + prednisone.


This was a preplanned analysis of data from 1,172 men receiving ADT+/- docetaxel +/- abiraterone acetate + prednisone. The analysis required a PSA at 8 months from ADT initiation, with a data cut off of June 1, 2021. rPFS and OS were assessed overall, and then by randomization groups. The analysis was performed for the following 8-month PSA cut-offs: 0.2 and 4 ng/ml. Additionally, median values of rPFS and OS were calculated from 8 months-PSA using the Kaplan Meier method.

PSA values at 8 months after ADT initiation were available in 931 men (79%). Standard of care was ADT + docetaxel in 62%, and 56% had “high volume” disease. The median follow-up was 4.4 years (95% CI 4.3-4.5). In the overall population, 8 month PSA > 0.2 vs <= 0.2 ng/mL was associated with worse rPFS in the ADT +/- docetaxel (median 1.4 years, 95% CI 1.2-1.7 vs 4.0 years, 95% CI 3.6 to not evaluable, p < 0.0001) and the ADT +/- docetaxel + abiraterone acetate + prednisone arms (2.2 years, 95% CI 1.6 to 2.9 vs median not evaluable, 95% CI 4.7 to not evaluable, p<0.0001):

psa_values-8_months_after_adt_initiation_graph_image_1

In the overall population, 8 month PSA > 0.2 vs <= 0.2 ng/mL was associated with worse OS in the ADT +/- docetaxel (median 3.5 years, 95% CI 3.1-4.1 vs not evaluable, 95% CI 4.8 to not evaluable, p<0.0001) and the ADT +/- docetaxel + abiraterone acetate + prednisone arms (3.4 years, 95% CI 2.8 to 3.9 vs not evaluable, 95% CI 5.7 to not evaluable, p<0.0001):

psa_values-8_months_after_adt_initiation_graph_image_2

In the ADT + docetaxel population, 8 month PSA > 0.2 vs <= 0.2 ng/mL was associated with worse OS in the ADT + docetaxel (median 3.5 years, 95% CI 2.8-4.0 vs not evaluable, 95% CI 4.0 to not evaluable, p = 0.0007) and the ADT + docetaxel + abiraterone acetate + prednisone arms (3.6 years, 95% CI 2.9 to not evaluable vs not evaluable, 95% CI 4.7 to not evaluable, p<0.0001):

psa_values-8_months_after_adt_initiation_graph_image_3

In the ADT + docetaxel population, 8 month PSA > 4 vs <= 4 ng/mL was associated with worse OS in the ADT + docetaxel (median 2.1 years, 95% CI 1.5 to 2.5 vs 4.5 years, 95% CI 4.0 to not evaluable, p < 0.0001) and the ADT + docetaxel + abiraterone acetate + prednisone arms (1.6 years, 95% CI 0.9 to 2.4 vs not evaluable, 95% CI 4.7 to not evaluable, p < 0.0001):

psa_values-8_months_after_adt_initiation_graph_image_4

Dr. Mescam concluded her presentation discussing 8-month PSA outcomes of men with mCSPC in the PEACE-1 trial with the following take-home messages:

  • 8-month PSA value strongly predicts both rPFS and OS in men with mCSPC in PEACE-1
  • There was a significantly higher number of patients that had a PSA <= 0.20 ng/mL with the combination of ADT + docetaxel + abiraterone acetate + prednisone arms versus ADT + docetaxel
  • Early therapeutic intervention in men with unfavorable 8-month PSA values needs to be investigated
  • The clinical and molecular characteristics of the population with elevated 8-month PSA values deserve better understanding

Presented by: Gwenaelle Gravis Mescam, Department of Medical Oncology, Institut Paoli-Calmettes, Aix-Marseille Université, Marseille, France

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2022 European Society of Medical Oncology (ESMO) Annual Hybrid Meeting, Paris, FR, Fri, Sept 9 – Tues, Sept 13, 2022. 

References:

  1. Fizazi K, Foulon S, Carles J, Roubaud G, et al. Abiraterone plus prednisone added to androgen deprivation therapy and docetaxel in de novo metastatic castration-sensitive prostate cancer (PEACE-1): A multicentre, open-label, randomized, phase 3 study with a 2 x 2 factorial design. Lancet. 2022 Apr 30;399(10336):1695-1707.