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ASCO GU 2021

ASCO GU 2021: Randomized Phase II Trial of Radium-223 plus Enzalutamide Versus Enzalutamide Alone in mCRPC: Final Efficacy and Safety Results

(UroToday.com) The clinical benefit of radium-223 has been demonstrated in patients with metastatic castration resistant prostate cancer (mCRPC) in the ALSYMPCA randomized placebo controlled trial.1 Over the last nearly decade since publication of this landmark trial, combination therapy in patients with mCRPC is of great interest for improving efficacy but must be done in a safe manner for these patients. Agarwal et al. previously reported that treatment with enzalutamide plus Radium-223 was associated with a decline in serum bone metabolism markers, which correlated with improved outcomes compared to enzalutamide alone.2 At the GU ASCO 2021 annual meeting, medical student Adam Kessel and colleagues presented results of the final efficacy and safety results for this trial.


In this phase 2 trial (NCT02199197), patients with progressive mCRPC were treated with enzalutamide (160 mg daily) +/- radium-223 (standard dose of 55 kBq/kg IV Q4 weeks x 6), until disease progression or unacceptable toxicities. The primary objectives of change in bone markers and safety have been reported previously.2 Secondary objectives included a comparison of PSA progression free survival, overall survival, and long-term safety in all patients receiving enzalutamide plus radium-223 versus enzalutamide alone. A post hoc analysis included a comparison of PSA-PFS2 (defined as time from the start of protocol therapy to PSA progression on subsequent therapy or death whichever occurred earlier), time to subsequent/next therapy, and long-term safety.

Between July 2014 and November 2017, 49 patients were eligible and enrolled in this trial. The median follow-up was 22 months (range 3.2-71.5) and 35 patients received enzalutamide plus radium-223 and 12 patients received enzalutamide alone. Receipt of prior abiraterone was allowed and was balanced between two groups: 60% in the enzalutamide plus radium-223 group versus 64% in the enzalutamide alone group. In the final efficacy results, time to subsequent/next therapy and PSA-PFS2 were significantly improved in the enzalutamide plus radium-223 patients over enzalutamide alone patients:

ASCO_GU_Radium-223.png



All other efficacy parameters (PSA-PFS, overall survival, and radiographic progression free survival) were numerically improved in enzalutamide plus radium-223 patients, but not statistically significant. With regards to the final safety results, none of the 12 enzalutamide alone patients had a fracture. There were two of 35 enzalutamide plus radium-223 patients found to have incidental grade 1 asymptomatic fracture at the site of bone metastasis on routine imaging, at 15 and 31 months, respectively after the last dose of radium-223, and did not require any intervention. No patients developed bone marrow disorders during the follow-up period.

Although a small, single institutional cohort, this study showed that enzalutamide plus radium-223 resulted in significant long-term clinical benefit over enzalutamide alone in patients with mCRPC without compromising safety.

Presented by: Adam Kessel, Huntsman Cancer Institute-University of Utah Health Care, Salt Lake City, UT

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia Twitter: @zklaassen_md during the 2021 ASCO Genitourinary Cancers Symposium (ASCO GU), February 11th to 13th, 2021


References:

  1. Parker C, Nilsson S, Heinrich D, et al. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med 2013;369(3):213-223.
  2. Agarwal N, Nussenzveig R, Hahn AW, et al. Prospective evaluation of bone metabolic markers as surrogate markers of response to radium-223 therapy in metastatic castration-resistant prostate cancer. Clin Cancer Res. 2020 May 1;26(9):2104-2110.