ASCO GU 2018: Real-world Study of Enzalutamide and Abiraterone Acetate (with Prednisone) Tolerability (REAAcT): Results

San Francisco, CA ( Oral enzalutamide and abiraterone (coadministered with prednisone), both androgen axis inhibitors introduced in the past decade, have had an immediate impact on the management of advanced prostate cancer. Approved for men with metastatic castration-resistant prostate cancer, demonstrating significant PFS, CCS and OS benefit, they have become commonly used in this setting. Recent studies have also begun to introduce them earlier in the PCa disease progression pathway, with the LATITUDE and STAMPEDE trials demonstrating benefit in the hormone-sensitive metastatic PCa setting.

However, despite their ubiquitous use, these medications have distinct adverse event profiles. From a clinician standpoint, it can often be a conundrum on which agent to use and how to sequence them.

In this large, multicenter, non-randomized real-world phase IV study (REAAcT), men with mCRPC who were initiated on Abi or Enza were followed prospectively to assess for tolerability. The decision to treat with Abi or Enza was up to the treating physician. All patients who were enrolled underwent baseline testing and testing 2 months after initiation of drug. Testing included primarily patient-reported outcomes (PROs) (EORTC QLQ 30, FACIT-Fatigue, FACT-Cog) and tests of 4 cognitive domains (Cogstate). Baseline Cogstate scores were used to estimate the rate of cognitive impairment - defined as ≥2SD from age-matched normative means of healthy males on ≥2 tests. Men were noted to have clinically meaningful cognitive change with a performance decline of |RCI|≥2 on ≥2 tests. Only men who completed both sets of evaluations and had no treatment protocol deviations were included in the analysis.

Of the 100 pts treated, 92 pts were evaluable due to assessment completion; Enza (n=46) and Abi (n=46). Median age for the cohort was 75 years. At baseline, characteristics and median scores were similar between arms, with mild cognitive impairment in approximately 20% of pts.
While drug discontinuation rates due to AEs were similar in both groups (1 Enza vs. 2 Abi pts), more dose reductions due to AEs occurred in patients taking Enza (16% vs. 6% Abi). Overall, men taking Enza also reported more adverse events (52% vs. 36%), but significant Grade 3/4 AEs (4% Enza vs. 6% Abi) were similar.

From a cognitive standpoint, unique neuropsychiatric AEs on Enza included amnesia, cognitive disorders, memory impairment, and confusional state; on Abi: cerebrovascular accident, presyncope, and spinal cord compression. Regarding fatigue, as has been historically reported, men on Enza had significantly more fatigue (26% vs. 8%). Four pts on Enza and 1 patient on Abi had clinically meaningful cognitive decline.

Based on these results, it would appear that despite starting at similar baseline values, men treated with enzalutamide have higher rates of fatigure and cognitive decline, though Grade ¾ AE’s were similar between both groups.

Taken in conjunction with recent data suggested that abiraterone should be sequenced first,1 perhaps the standard of care should be abiraterone + prednisone prior to enzalutamide, unless there are specific contraindications.

Limitations / Discussion Points:
1. This is a small cohort of only 100 patients. For a phase IV study, this is somewhat miniscule.
2. 2 months may not be sufficient follow-up. Longer follow-up may reveal different results. As many of these men are on these medications for months to years, longer follow-up should be assessed.

Speaker: Neal Shore, MD

Co-Authors: Daniel R. Saltzstein, Paul R. Sieber, Bryan Mehlhaff, Lawrence Gervasi, Jennifer Phillips, Yu-Ning Wong, Huiling Pei, Tracy McGowan

Institution(s): Atlantic Urology, Myrtle Beach, SC; Urology San Antonio, San Antonio, TX; Lancaster Urology, Lancaster, PA; Oregon Urology Institute, Springfield, OR; Southwest Urology, LLC, Cleveland, OH; Janssen Scientific Affairs, LLC, Horsham, PA; Janssen Research & Development, LLC, Spring House, PA

Written by: Thenappan Chandrasekar, MD, Clinical Fellow, University of Toronto, Twitter: @tchandra_uromd at the 2018 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, February 8-10, 2018 - San Francisco, CA

1. Wallis CJD, Klaassen Z, Bhindi B, Goldberg H, Chandrasekar T, Farrell AM, Boorjian SA, Kulkarni GS, Karnes RJ, Satkunasivam R. Comparison of Abiraterone Acetate and Docetaxel with Androgen Deprivation Therapy in High-risk and Metastatic Hormone-naïve Prostate Cancer: A Systematic Review and Network Meta-analysis. Eur Urol. 2017 Oct 13. pii: S0302-2838(17)30849-7. doi: 10.1016/j.eururo.2017.10.002. [Epub ahead of print] Review.