Written By: Samantha Larson, PharmD, M Health Fairview
Positive Quality Intervention: Enzalutamide (Xtandi) In Castration-Resistant Prostate Cancer or Metastatic Castration-Sensitive Prostate Cancer
Description: The purpose of this PQI is a summary of process for initiating and monitoring enzalutamide therapy in patients with either castration-resistant prostate cancer or metastatic castration-sensitive prostate cancer (mCSPC).1
Background: Enzalutamide is a pure androgen receptor inhibitor approved in August of 2012 for the treatment of castration-resistant prostate cancer. It gained approval for metastatic castration-sensitive prostate cancer in December of 2019. The efficacy in patients with either castration-sensitive or castration-resistant prostate cancer was demonstrated in 5 major clinical trials: AFFIRM, PREVAIL, TERRAIN, PROSPER, ARCHES (see Supplemental Information section). Enzalutamide therapy in mCSPC is recommended both by National Comprehensive Cancer Network (Category 1)9 and American Urological Association Guidelines (Strong Recommendation; Evidence Level: Grade A)8 however is underutilized among new patients both in oncology and urology settings. Enzalutamide use in mCSPC should be considered as a potential and evidence-based option.
PQI Process: Identify patients of CRPC and mCSPC and evaluate eligibility for second-generation anti-androgens such as enzalutamide. Upon receipt of a new prescription for enzalutamide for prostate cancer:
- Initial dosing for all indications is 160 mg once daily
- Available as 40 mg tablets, 40 mg capsules, or 80 mg tablets
- Swallow capsules or tablets whole
- Patients should also receive a gonadotropin-releasing hormone (GnRH) analog concurrently or should have had bilateral orchiectomy
- Reduce enzalutamide dose accordingly if co-administered with:
- Strong CYP2C8 inhibitors – 80 mg daily
- Strong CYP3A4 inducers – 160 mg to 240 mg once daily
- Monitor LFTs at baseline and periodically throughout duration of therapy
- Monitor blood pressure at baseline and throughout therapy
- Dose modifications
- Grade ≥3 toxicity or intolerable side effects, withhold dosing for 1 week or until symptoms improve to ≤ Grade 2, then resume at the same dose or a reduced dose (120 mg or 80 mg), if warranted
- Review concomitant anticoagulation medications and adjust accordingly7
Patient Centered Activities:
- Provide Oral Chemotherapy Education (OCE) Sheet
- Administration: Can be taken with or without food at the same time once daily
- Review baseline labs and chronic medications – dose adjustment needed with concomitant CYP3A4 inducers or CYP2C8 inhibitors
- Storage: Store at room temperature in the original bottle; do not remove desiccant from bottle
- Xtandi (enzalutamide) [prescribing information]. New York, NY: Astellas Pharma US, Inc; 2020.
- Fizazi K, Scher HI, Miller K, Basch E, Sternberg CN, Cella D, Forer D, Hirmand M, de Bono JS. Effect of enzalutamide on time to first skeletal-related event, pain, and quality of life in men with castration-resistant prostate cancer: results from the randomised, phase 3 AFFIRM trial. Lancet Oncol. 2014 Sep;15(10):1147-56. doi: 10.1016/S1470-2045(14)70303-1. Epub 2014 Aug 4. Erratum in: Lancet Oncol. 2014 Oct;15(11):e475. PMID: 25104109.
- Beer TM, Armstrong AJ, Rathkopf D, et al. Enzalutamide in men with chemotherapy-naïve metastatic castration-resistant prostate cancer: extended analysis of the phase 3 PREVAIL study. Eur Urol 2017;71(2):151-4.
- Shore ND, Chowdhury S, Villers A, et al. Efficacy and safety of enzalutamide versus bicalutamide for patients with metastatic prostate cancer (TERRAIN): a randomized, double-blind, phase 2 study. Lancet Oncol 2016;17(2):153-63.
- Hussain M, Fizazi K, Saad F, et al. Enzalutamide in men with nonmetastatic, castration-resistant prostate cancer. N Engl J Med 2018;378(26):2465-74.
- Armstrong AJ, Szmulewitz RZ, Petrylak DP, et al: ARCHES: A randomized, phase III study of androgen-deprivation therapy with enzalutamide or placebo in men with metastatic hormone-sensitive prostate cancer. J Clin Oncol 37:2974-2986, 2019
- Shatzel JJ, Daughety MM, Olson SR, et al. Management of Anticoagulation in Patients With Prostate Cancer Receiving Enzalutamide. J Onco Prac 2017;13(11):720-728.
- Lowrance WT, Breau RH, Chou R et al: Advanced Prostate Cancer: AUA/ASTRO/SUO Guideline PART I. J Urol 2021; 205: 14
- NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Prostate Cancer V.2.2021. © National Comprehensive Cancer Network, Inc. 2020. All rights reserved. Accessed 2-15-2021.
Xtandi Support Solutions®: Patient Support program
- Enroll online or by calling 1-855-8XTANDI (1-855-898-2634)
- Benefits Verification
- Prior Authorization and Denial Appeals Assistance
- XTANDI Quick Start+® Program
- XTANDI Patient Savings Program
- Astellas Patient Assistance Program
- Financial Assistance Information for Medicare Patients
|Patient Population||mCRPC||mCRPC||mCRPC||Nonmetastatic CRPC||mCSPC|
|Study Design||Enzalutamide + LHRH therapy (n=800)|
vs placebo LHRH therapy (n=399)
|Enzalutamide + LHRH therapy (n=872)|
vs placebo LHRH therapy (n=845)
|Enzalutamide + LHRH therapy (n=184)|
Vs. bicalutamide + LHRH therapy (n=191)
|Enzalutamide + LHRH therapy (n=933)|
vs placebo LHRH therapy (n=468)
|Enzalutamide + LHRH therapy (n=574)|
vs placebo LHRH therapy
|Outcomes||Median time to first skeletal event: Enzalutamide 16.7 months vs placebo 13.3 months|
Pain progression at week 13: Enzalutamide 28% vs. placebo 39%
|Median overall survival: Enzalutamide 35.3 months vs placebo 31.3 months|
Median radiographic progression-free survival: Not reached with enzalutamide + LHRH therapy vs 3.7 months with placebo + LHRH therapy
|Median radiographic progression-free survival: Enzalutamide group 19.5 months vs bicalutamide group 13.4 months|
Median progression-free survival: Enzalutamide patients 15.7 months and bicalutamide patients 5.8 months
|Median metastasis-free survival: 3 years with enzalutamide therapy vs 14.7 months with placebo|
First use of subsequent prostate cancer therapy was delayed by: Median of 3 years with enzalutamide + LHRH therapy vs. 17.7 months with placebo + LHRH therapy
|Risk of radiographic disease progression or death:|
61% reduction with enzalutamide + LHRH therapy vs placebo + LHRH therapy
Risk of starting a new antineoplastic therapy: 72% reduction with
enzalutamide + LHRH therapy vs placebo + LHRH therapy
*mCRPC-metastatic castration-resistant prostate cancer, LHRH-luteinizing hormone-releasing hormone, CRPC-castration-resistant prostate cancer, mCSPC – metastatic castration-sensitive prostate cancer