Page 2 - nmCRPC Clinical Support Tool-MARCH2021

nmCRPC Trials – Health-related Quality of LifenmCRPC Trials – Health-related Quality of Life
Men with nmCRPC generally have good quality of life (QoL), and it is important that they be able to maintain that
level of QoL for as long as possible. In each of the nmCRPC AR-targeted therapy trials, health-related QoL was
maintained following treatment initiation:

PROSPER
SPARTAN 5 8 SPARTAN 5 3 PROSPER 6 PROSPER 9 6 4 ARAMIS 4
SPARTAN
ARAMIS
ARAMIS
FACT-P total score (treatment difference in least squares FACT-P total score (treatment difference in least squares
FACT-P Total Score (treatment difference in least squares mean FACT-P Total Score (treatment difference in least squares mean
FACT-P Total Score
FACT-P Total Score (treatment difference in least squares mean change from baseline) FACT-P Total Score (treatment difference in least squares FACT-P Total Score
FACT-P Total Score
mean change from baseline)
change from baseline)
(difference vs. placebo)
mean change from baseline) change from baseline) mean change from baseline) (difference vs. placebo)
1.3 (0.4, 2.1) 1.3 (0.4, 2.1) 1.3 (0.4, 2.1)
7 6 5 4 ENZA + ADT Placebo + ADT 7 6 5 4 ENZA + ADT 120 p < 0.01 120 p < 0.01
p < 0.01
Least Squares Mean (SD) Change from Baseline -2.0 0 Least Squares Mean (SD) Change from Baseline -2.0 0 Least Squares Mean (95% Cl) Treatment Difference 110 - Favours Favours Placebo +ADT Least Squares Mean (95% Cl) Treatment Difference -1 3 2 1 0 Favours Favours Placebo +ADT 110 110
Apalutamide + ADT
Placebo + ADT
Apalutamide + ADT
2.0
2.0
120 -
3
90
90
2
100 -
80
1
80
0 90 -
70
70
-1 80 -
60
60
-2
-2
70 -
-3
-3
50
50
-4.0
-4.0
60 -
-5 50 -
-5
30
30
-6 40 -
-6
-6.0
20
20
-7
-7 30 -
29
2 3 4 5 6 7 9 11 13 17 -6.0 21 2 25 3 29 4 5 FACT-P Total Score 6 -4 7 Baseline 11 17 13 17 33 21 25 49 65 -4 Ba 81seline 9717 33 FACT-P Total Score 40 49 65 81 97 FACT-P Total Score 40
9
20 - 10 10
Treatment Cycle* 10 - Study Week 0 Study Week 0
Treatment Cycle*
No. of patients in each cycle No. of patients in each cycle No. at risk
No. at risk 0 -
Darolutamide Placebo Darolutamide Placebo Darolutamide Placebo
*Cycle 29 is approximately 25.8 months from the start of treatment. Minimum clinically important difference, 10 points
*Cycle 29 is approximately 25.8 months from the start of treatment.*Cycle 29 is approximately 25.8 months from the start of treatment.
FACT-P = Functional Assessment of Cancer Therapy – Prostate
FACT-P = Functional Assessment of Cancer Therapy – ProstateFACT-P = Functional Assessment of Cancer Therapy – Prostate 1. Saad F, et al. Lancet Oncol 2018;19:1404-16 1. Saad F, et al. Lancet Oncol 2018;19:1404-16
Minimum clinically important difference, 10 points Minimum clinically important difference, 10 points 2. Tombal B, et al. Lancet Oncol 2019;20:556-9 2. Tombal B, et al. Lancet Oncol 2019;20:556-9
QoL = Quality of life
Each of the AR-targeted therapies is associated with a 3. Fizazi K, et al. 2019;380:1235-46 3. Fizazi K, et al. 2019;380:1235-46
QoL = Quality of life
different adverse event (AE) profile:
Adverse events (AEs) in the phase 3 trials of AR-targeted therapies:
SPARTAN 5 ARAMIS 6 PROSPER 7 Dosing and monitoring requirements differ slightly
All Grades (%) All Grades (%) All Grades (%) among the three AR-targeted therapies:
Apalutamide Placebo Darolutamide Placebo Enzalutamide Placebo
(n = 803) (n = 398) (n = 954) (n = 554) (n = 930) (n = 465) Dosage and administration:
AE leading to 15 7.3 8.9 8.7 17 9
discontinuation Apalutamide 10
Hypertension 28 21 7.8 6.5 18 6
• 240 mg (four 60 mg tablets) taken orally, once daily
Rash 26 6.3 3.1 1.1 4 3 • Swallow tablets whole with a glass of water
Fatigue 33 21 13.2 8.3 46 22 • Can be taken with or without food
Fracture 18 7.5 5.5 3.6 18 6
Darolutamide 11
Fall 22 9.5 5.2 4.9 18 5
• 600 mg (two 300 mg film-coated tablets) taken orally,
Seizure 0.6 0 0.2 0.2 < 1 0
twice daily
Hypothyroidism 9.8 2.0 NR NR NR NR • Swallow tablets whole with food
Diarrhea 23 15 7.4 5.6 12 10
Nausea 20 16 5.6 5.8 13 9 Enzalutamide 12
Arthralgia 20 8.3 9.0 9.4 13 8 • 160 mg (four 40 mg capsules) taken orally, once daily
• Swallow capsules whole with a glass of water
Durations of treatment differed, and scheduled study visits for AEs occurred with
different frequencies across trials. Therefore, the data in this table are not meant • Can be taken with or without food
for cross-trial comparison. NR = Not reported
Patient Monitoring
In general, AR-targeted therapies require minimal monitoring. All patients should undergo monitoring for laboratory or clinical
parameters as per routine clinical practice. 10-12
Apalutamide 10 • Patients taking warfarin should have their international
• Measure thyroid-stimulating hormone levels during the normalized ratio measured at baseline and at each visit.
treatment of hypothyroidism. Enzalutamide 12
• Assess risk of fracture or fall and treat to prevent clinical • Measure blood pressure at baseline and periodically
fractures according to national guidelines (consider use during treatment.
of bone-targeted agents). • Consider electrocardiogram monitoring at baseline and
• Assess those with a cardiac history for active cardiac during treatment for patients at risk for QTc prolongation
disease before and during apalutamide treatment. or taking medications known to prolong the QTc interval.
• Consider electrocardiogram monitoring at baseline and • Patients taking warfarin should have their international
during treatment for patients at risk for QTc prolongation normalized ratio measured at baseline and at each visit.
or taking medications known to prolong the QTc interval.
The following chart summarizes the CUA’s recommended
approach to the treatment of nmCRPC, including the use
of the available AR-targeted treatments:
CUA Approach to nmCRPC 15
* At the time of the guidelines publication, darolutamide was not yet approved in Canada; however, it was acknowledged that darolutamide was tested in a similar
patient population of high-risk nmCRPC with positive results.
Drug Interactions
Patients with nmCRPC often have comorbidities requiring several drug treatments. AR-targeted treatments are associated with
drug-drug interactions. 10-14 Please consult a pharmacist for specific interactions.
References
1. ClinicalTrials.gov Identifier: NCT01946204 9. Tombal B, et al. Lancet Oncol 2019;20:556–9
2. Smith MR, et al. N Engl J Med 2018;378:1408–18 10. ERLEADA (apalutamide) Product Monograph, 2020
®
3. Fizazi K, et al. N Engl J Med 2019;380:1235–46 11. NUBEQA (darolutamide) Product Monograph, 2020
®
4. Hussain M, et al. N Engl J Med 2018;378:2465–74 12. XTANDI (enzalutamide) Product Monograph, 2020
®
5. Smith MR, et al. Eur Urol 2021;79:150–8. 13. FDA. https://www.fda.gov/Drugs/DevelopmentApprovalProcess/
6. Fizazi K, et al. N Engl J Med 2020;383:1040–9. DevelopmentResources/DrugInteractionsLabeling/ucm093664.htm
7. Sternberg CN, et al. N Engl J Med 2020;382:2197–206. 14. Lexicomp Online, Pediatric and Neonatal Lexi-Drugs Online, 2020
8. Saad F, et al. Lancet Oncol 2018;19:1404–16 15. Saad F, et al. Can Urol Assoc J 2019;13:307–14

NBQ016E
PP-NUB-CA-0109-1
This tool has been developed through an unrestricted educational grant from Bayer Inc. January, 2021