(UroToday.com) The 2023 ESMO annual meeting included a session on prostate cancer, featuring a presentation by Dr. Bertrand Tombal discussing combination treatment with radium-223 and enzalutamide in patients with metastatic castration-resistant prostate cancer (mCRPC) in the REASSURE study.
Indeed, both radium-223 and enzalutamide prolong overall survival (OS) in patients with mCRPC.1,2 However, their different mechanisms of action and non-overlapping safety profiles make them attractive combination partners. Treatment intensification with two distinct drugs may lead to improved and more durable disease control. At the 2023 ESMO annual meeting, Dr. Tombal and colleagues presented clinical outcomes of patients who received combined or layered treatment with radium-223 and enzalutamide in REASSURE, a global, prospective, observational study of radium-223 use in patients with mCRPC.
Data from 1,465 patients were analyzed, which included patient subgroups (i) “combined” (patients started radium-223 and enzalutamide within 30 days of each other, n=46) and (ii) “layered” (patients started radium-223 >30 days after starting enzalutamide or vice versa, n=205). The REASSURE study design is as follows:
The complete baseline characteristics for patients included in this study are as follows:
The proportions of patients who had completed ≥1 life-prolonging therapy for mCRPC prior to radium-223 were 43%, 52%, and 61% in the combined, layered, and all patient groups, respectively. Furthermore, 30%, 27%, and 33% had received prior abiraterone, and 17%, 29% and 36% had received prior docetaxel, respectively:
More patients in the combined group (74%) completed six cycles of radium-223 than in the layered (61%) or all patient (59%) groups. The median duration of observation from start of radium-223 for combined, layered, and all patient groups was 17.3, 11.1, and 11.5 months, respectively. The proportions of patients with a ≥30% decline in alkaline phosphatase at week 12 were 58%, 41%, and 47% in the combined, layered, and all patient groups, respectively. The corresponding values for a ≥30% decline in PSA were 54%, 17%, and 20%, respectively. The median OS was 22.2 months (95% CI 13.7–26.8) in the combined group, 16.5 months (95% CI 13.9–19.5) in the layered group, and 15.6 months (95% CI 14.6–16.5) in all patient groups:
Among men receiving bone health agents, those in the combined group had a higher proportion of fractures (8%), compared to all patients (3%) and layered group patients (2%). However, when patients did not receive concomitant bone health agents, the fracture risk was 6% for all patients, 5% for the combined group, and 4% for the layered group. With regards to adverse events, they were quite similar between groups. However, 28% of patients in the layered group had treatment emergent drug-related adverse events, compared to 35% among all patients, and 37% among combined patients:
Dr. Tombal concluded his presentation discussing combination treatment with radium-223 and enzalutamide in patients with mCRPC in the REASSURE study with the following concluding statements:
- In this real-world study, when combined or layered with enzalutamide, treatment with radium-223 was not associated with new safety signals and did not appear to increase fracture risk
- Median OS was numerically longer in the combined versus the layered group or all patient group
- A phase 3 trial (PEACE III, NCT02194842) investigating the combination of enzalutamide with radium-223 is ongoing (estimated first completion date: March 2024)
Presented by: Bertrand Tombal, MD, PhD, Cliniques Universitaires Saint-Luc, Woluwe-Saint-Lambert, Belgium
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2023 European Society of Medical Oncology (ESMO) Annual Meeting, Madrid, Spain, Fri, Oct 20 – Tues, Oct 24, 2023.
References:
- Beer TM, Armstrong AJ, Rathkopf DE, et al. Enzalutamide in metastatic prostate cancer before chemotherapy. N Engl J Med 2014;371(5):424-433.
- 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.