ASCO GU 2021: Real-World Clinical Outcomes Study of Sequential Novel Antihormonal Therapy (NAH) or Ra-223 Treatment of mCRPC That Progressed After First-Line NAH

( The field of advanced prostate cancer has rapidly progressed over the past 15 years. Prior to the publication of TAX-327, there were no proven life-prolonging therapies for patients with metastatic castration-resistant prostate cancer (mCRPC). Since that time, there have been many new agents that have proven survival benefits including taxane-based chemotherapy, agents targeting the androgen axis, and bone-targeting agents. The optimal sequencing of these agents is somewhat unclear. Thus, to inform these decisions, Dr. Oliver Sartor and colleagues assessed real-life clinical outcomes in patients with mCRPC treated in the USA who received sequential first-line (1L)/second-line (2L) NAH (abiraterone/enzalutamide or enzalutamide/abiraterone) or switched to a different mechanism of action (alpha-emitter Ra-223) after progression on 1L NAH as presented in a plenary abstract presentation in the Poster Highlights Session: Prostate Cancer session at the 2021 ASCO GU Cancers Symposium.

The authors retrospectively reviewed the Flatiron electronic health record database to identify patients with mCRPC who progressed on 1L NAH and started 2L monotherapy with Ra-223 (n=120) or NAH (n=226) between January 2013 and December 2018. The authors then descriptively characterized patient characteristics, overall survival (OS) from the start of second-line therapy, and symptomatic skeletal events (SSEs).

Patients who received a second NAH and those who switched to Ra-223 had generally similar characteristics at the time of initiating second-line therapy, including similar rates of bone-health agents. However, patients who initiated Ra-223 in the second-line setting had a higher incidence of bone-only metastases, a shorter duration of first-line NAH, and a higher rate of prior SSEs than the second-line NAH cohort.

From the start of second-line therapy, the median duration of second-line therapy was 5.6 months (median 4.5 doses) for patients receiving Ra-223 and 4.7 months for patients receiving second-line NAH. Median overall survival from the start of second-line therapy was 10.8 months for patients receiving Ra-223 and 11.2 months for patients receiving second-line NAH, with 49% and 39%, respectively, receiving subsequent therapy.


Among those who received subsequent therapy after the second-line setting, the use of subsequent taxanes was lower in the Ra-223 cohort (47%) than in the second-line NAH cohort (76%).


After the start of second-line therapy, SSEs were observed starting in 32 patients (27%) on Ra-223 and 49 (22%) on second-line NAH.

On the basis of these data, the authors conclude that overall survival is similar in these two subgroups of patients with mCRPC (hazard ratio 1.26, 95% confidence interval 0.92 to 1.74).


Presented by: Oliver A. Sartor, MD, Professor of Medicine; Medical Director, Tulane Cancer Center; C. E. and Bernadine Laborde Professor of Cancer Research in New Orleans, LA

Co-Authors: Daniel J. George, Bertrand Tombal, Celestia S. Higano, Cora N. Sternberg, Kurt Miller, Xiaolong Jiao, Helen Guo, Per Sandstrom, Frank Verholen, Fred Saad, Neal D. Shore

Written by: Christopher J.D. Wallis, Urologic Oncology Fellow, Vanderbilt University Medical Center Twitter @WallisCJD during the 2021 ASCO Genitourinary Cancers Symposium (ASCO GU), February 11th to 13th, 2021