(UroToday.com) At the 2021 American Urologic Association (AUA) annual meeting, Dr. Michael Fabrizio discussed real-world utilization of apalutamide and enzalutamide in non-metastatic castrate resistant prostate cancer. Management of non-metastatic castrate-resistant prostate cancer has shifted since the approval of three second-generation androgen receptor antagonists: apalutamide, enzalutamide, and darolutamide. In clinical trials, all agents have proven to delay metastases, with discontinuation rates due to adverse events in 15% of apalutamide patients, 17% of enzalutamide patients, an 9% of darolutamide patients.1-3 However, real-world data on these agents is lacking. Dr. Fabrizio and colleagues aimed to assess the real-world utilization of two of these new agents (apalutamide and enzalutamide) among non-metastatic castrate-resistant prostate cancer patients from urology electronic medical records database.
In this study, patients diagnosed with non-metastatic castrate-resistant prostate cancer who initiated apalutamide or enzalutamide as an initial androgen receptor antagonist from February 1, 2018, to September 30, 2020, were retrospectively identified from the Precision Point Specialty (PPS) Analytics Portal for Prostate Cancer, a database containing electronic medical records for over 80 active community urology practices. Due to launch timing, data on darolutamide was not yet available and thus excluded from the study. Patient demographics, clinical characteristics, and utilization patterns were reviewed. Survival analyses were used to describe time to discontinuation. A supplemental chart review was conducted to identify reasons for dose reduction and discontinuation.
A total of 2,636 patients were identified, 1,023 (39%) men receiving apalutamide and 1,613 (61%) receiving enzalutamide. The mean age at initiation was 77.8 years with 68% of patients self-reporting race as white. There were 73% of patients that had a Charlson Comorbidity Index score of 0. The median PSA was 3.7 ng/dl for apalutamide and 4.1 ng/dl for enzalutamide. The median duration of follow-up was 18.7 months for apalutamide and 12.1 months for enzalutamide, with a median therapy duration of 12.9 and 9.8 months for apalutamide and enzalutamide, respectively. More than 41% of patients discontinued use of initial androgen receptor antagonist, with another 9.4% switching therapy. The median time to discontinuation was 9.0 months for apalutamide and 7.4 months for enzalutamide, and the median time to switch was 4.8 months for apalutamide and 6.5 months for enzalutamide:
A patient subset was randomly selected for chart review (n = 977; 455 apalutamide and 522 enzalutamide). The most common reason reported for drug discontinuation and switch was adverse events at 50% (43.4% of apalutamide patients and 58.2% of enzalutamide patients):
Among the 5.6% of patients that had dose reduction, 72.4% apalutamide and 73.1% enzalutamide patients reported the most common reason as adverse events. One of the main limitations of this study was that due to the timing of the study start date, there was a lack of follow-up data available for darolutamide for outcome analysis such as discontinuation of treatment.
Dr. Fabrizio concluded his presentation of apalutamide and enzalutamide use among non-metastatic castrate-resistant prostate cancer in the real-world setting with the following take-home messages:
- There was a high incidence of androgen receptor antagonist discontinuation (41.2%) and among them 50% of patients reported adverse events as the primary reason for discontinuing therapy or switching
- Discontinuation rates due to adverse events were 28% higher (43% versus 15%) among those treated with apalutamide and 41% higher (58% vs 17%) among enzalutamide patients in the real-world compared to clinical trials
- The subset of patients with dose reduction also reported adverse events as the primary reason (72.7%) for needing to reduce the dose
- These results show the need for additional therapies with improved safety profiles and warrants future studies with all non-metastatic castrate-resistant prostate cancer agents
Presented by: Michael Fabrizio, MD, FACS, Eastern Virginia Medical School, Norfolk, VA
Co-Authors: Sreevalsa Appukkuttan, Keely Madaj, Yuxian Du, John Azzolina, Wanda Wilt, Jacqueline Parkin, Jamie Partridge, Sheldon Kong
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 2021 American Urological Association, (AUA) Annual Meeting, Fri, Sep 10, 2021 – Mon, Sep 13, 2021.
References:
- Smith MR, Saad F, Chowdhury S, et al. Apalutamide treatment and metastasis-free survival in prostate cancer. N Engl J Med 2018;378(15):1408-1418.
- Hussain M, Fizazi K, Saad F, et al. Enzalutamide in men with nonmetastatic, castration-resistant prostate cancer. N Engl J Med. 2018 Jun 28;378(26):2465-2474.
- Fizazi K, Shore N, Tammela TL, et al. Darolutamide in nonmetastatic castration-resistant prostate cancer. N Engl J Med. 2019;380(13):1235-1246.