Page: 1 | April 12, 2023
A Journal Article Review: “Enzalutamide in Metastatic Prostate Cancer before Chemotherapy”Beer T.M., Armstrong A.J., Rathkopf D.E., et al. N Engl J Med 2014; 371:424-433
Jenna Gianninoto, PharmD, CSPAvella Specialty Pharmacy
Page: 2 | April 12, 2023
Disclaimer
• The information is for educational purposes only, and is not
intended to substitute for the medical judgment of the healthcare
provider. Recommendations for use of any particular therapeutic
agents or methods are based upon the best available scientific
evidence and clinical guidelines. Reference in this activity to any
specific commercial products, process, service, manufacturer, or
company does not constitute its endorsement or
recommendation. Off-label use of therapeutic agents will be
discussed.
Page: 3 | April 12, 2023
Disclosure
• Dr. Gianninoto serves as a compensated employee of Avella Specialty Pharmacy.
Page: 4 | April 12, 2023
Pharmacologic Treatment of Prostate Cancer
• LHRH agonists
• LHRH antagonists
• Chemotherapy
• Anti-androgens
Page: 5 | April 12, 2023
Abiraterone • MOA
– Selectively and irreversibly inhibits CYP17
– Inhibits the formation of the testosterone precursors
• Indication – Treatment of metastatic
castration-resistant prostate cancer in combination with prednisone
Zytiga [package insert] Janssen Biotech Inc.
Page: 6 | April 12, 2023
Abiraterone
• Administration and dosage – 1000mg once daily
• Common ADE– Joint swelling, hypokalemia,
edema, muscle discomfort, hot flush, diarrhea, urinary tract infection, cough, hypertension, arrhythmia, urinary frequency, nocturia, dyspepsia, and upper respiratory tract infection.
• “Abiraterone in Metastatic Prostate Cancer without Previous Chemotherapy”– Improved radiographic PFS– Improved overall survival – Safety profile similar to
what was previously reported
Zytiga [package insert] Janssen Biotech Inc.Ryan C.J., Smith M.R., de Bono J.S., et al. N Engl J Med 2013; 368:138-148
Page: 7 | April 12, 2023
Enzalutamide• MOA
– Androgen receptor inhibitor – Competitively inhibits
androgen binding to receptors and inhibits androgen receptor nuclear translocation and interaction with DNA
• Indication – Treatment of patients with
metastatic castration-resistant prostate cancer who have previously received docetaxel
Xtandi [package insert] Astellas Pharma Inc.
Page: 8 | April 12, 2023
Enzalutamide
• Dosage and administration– 160mg (four 40mg capsules) by mouth once daily– Administered with or without food – No initial dosage adjustments for mild to moderate
renal or hepatic impairment is necessary – Store at room temperature
Page: 9 | April 12, 2023
Enzalutamide
• Common ADE– Asthenic conditions– Anxiety– Diarrhea– Dizziness– Hot Flush– Hypertension – Insomnia– Musculoskeletal pain– Peripheral edema– Respiratory tract
infection
• Warnings– Seizure
• In clinical trials, 0.9% of patients treated with enzalutamide experienced a seizure.
– Fertility impairment • Male fertility may be
impaired with treatment
Page: 10 | April 12, 2023
Enzalutamide
• Drug-Drug Interactions – Metabolized via CYP 3A4 and 2C8
• 3A4 – Strong/moderate inducers: carbamazepine,
phenytoin– Strong/moderate inhibitors: itraconazole
• 2C8 – Strong/moderate inducers: rifampin– Strong/moderate inhibitors: gemfibrozil
Page: 11 | April 12, 2023
“Enzalutamide in Metastatic Prostate Cancer before Chemotherapy”
Beer T.M., Armstrong A.J., Rathkopf D.E., et al. N Engl J Med 2014; 371:424-433
• Study Design– Double-blind, randomized, placebo controlled– Phase three trial– From September 2010 to September 2012
1717 patients enrolled in the study– 207 sites globally
Page: 12 | April 12, 2023
Primary and Secondary Endpoints
• Co-primary endpoints– Radiographic progression-free survival– Overall survival
• Secondary endpoints– Time until initiation of cytotoxic chemotherapy– Time until the first skeletal-related event– Best overall soft-tissue response– Time until PSA progression– Decline in PSA level of 50% or more from baseline
Page: 13 | April 12, 2023
Statistical Analysis
• Goal for enrollment was ~1680 patients
• Co-primary endpoints analyzed in the intention-to-treat population – Total type I error rate of 0.05
• Secondary endpoints analyzed using Holm’s step-down procedure
Page: 14 | April 12, 2023
Participants
• Eligibility criteria – Adenocarcinoma of the prostate with documented
metastases – PSA and/or radiographic progression in bone or soft
tissue– Prior therapy – Eastern Cooperative Oncology Group performance status– Asymptomatic or mildly symptomatic disease
• Exclusion criteria – Seizure
Page: 15 | April 12, 2023
Results
Page: 16 | April 12, 2023
Page: 17 | April 12, 2023
Page: 18 | April 12, 2023
Page: 19 | April 12, 2023
Clinical Significance
• Option for patients with metastatic prostate cancer prior to chemotherapy use
• Safety profile similar to previously reported
• Significantly delayed – Radiographic disease progression or death– The need for cytotoxic chemotherapy– Deterioration in quality of life and significantly
improved overall survival
Page: 20 | April 12, 2023
Specialty versus Retail
Retail Specialty
Patient Contact Reactive Proactive
Drug Availability Limited Carried in stock
Clinical support Limited knowledge about lots of drugs Specialized knowledge
Availability of clinical staff Regular hours 24/7
Dispensing vs. patient care Low patient contact High Touch
Adherence/Persistence Tools Limited to none Numerous
Billing Multiple challenges Split Billing
Financial Assistance/PA’s Limited to none Core service
Page: 21 | April 12, 2023
The Path of a Specialty Prescription
Retail Rx
Specialty Rx
Page: 22 | April 12, 2023
Jenna Gianninoto, PharmD, CSP
(877)792-7684 ext.3819
Top Related