Cost per median overall survival month associated with abiraterone acetate and enzalutamide for treatment of patients with metastatic castration-resistant prostate cancer

Figures & data

Table 1. Study-design criteria for studies COU-AA-302 and PREVAIL.

	COU-AA-302^7	PREVAIL^9
Study drug	Abiraterone acetate plus prednisone vs placebo plus prednisone	Enzalutamide vs placebo
Sample size	1088	1717
Randomization	1:1	1:1
Disease progression  criteria	PSA according to PCWG2 or radiographic progression according to modified RECIST criteria	At least one of the following: • Rising PSA levels at least 1 week apart • Soft tissue disease progression defined by RECIST 1.1 • Bone disease progression defined by PCWG2, with at least 2 new lesions on bone scan^a
Disease status	Asymptomatic or mildly symptomatic based on BPI-SF	Asymptomatic or mildly symptomatic based on BPI-SF
Baseline ECOG-PS	0–1	0–1
Interim analysis plan	3 interim analyses	1 interim analysis
Final analysis	773 deaths	765 deaths
Stopping rule	Radiographic progression with unequivocal clinical progression^b	Treated until confirmed radiographic progression or skeletal-related event and initiation of cytotoxic chemotherapy or alternate investigational agent for prostate cancer

a Patients who received an anti-androgen must have had progression after withdrawal (at least 4 weeks since last flutamide dose or at least 6 weeks since last bicalutamide or nilutamide dose). PSA value at the screening visit had to be ≥2 ng/mL.

b Unequivocal clinical progression was characterized as follows: cancer pain requiring initiation of chronic opiate analgesia, initiation of cytotoxic chemotherapy, radiation or surgical intervention due to tumor progression, or ECOG status ≥3.

BPI-SP, Brief Pain Inventory–Short Form; ECOG-PS, Eastern Cooperative Oncology Group performance status; PCWG2, Prostate Cancer Working Group 2; PSA, Prostate-specific antigen; RECIST, Response Evaluation Criteria in Solid Tumors.

Table 2. Baseline characteristics of COU-AA-302 and PREVAIL populations.

	COU-AA-302^7^,^13^,^14		PREVAIL^9
Intent-to-treat population, n	1088		1717
Active/placebo	Abiraterone acetate + prednisone	Placebo + prednisone	Enzalutamide	Placebo
Intent-to-treat population, n	546	542	872	845
Median age, years (range)	71 (44–95)	70 (44–90)	72 (43–93)	71 (42–93)
Gleason score ≥8 at initial diagnosis	54%	50%	51%	52%
ECOG-PS of 0	76%	76%	67%	69%
Baseline pain 0–1 on BPI-SF Q3	66%	64%	66%	68%
Baseline use of corticosteroids	NR	NR	4.0%	4.3%
Median time from initial diagnosis to first dose, years	5.5	5.1	NR	NR
Median PSA, ng/mL	42.0	37.7	54.1	44.2
Median LDH, IU/L	187.0	184.0	185.0	185.0
Bone disease	83%	80%	85%	82%
>10 bone metastases	49%	47%	33%	32%
Soft tissue disease	49%	50%	59%	60%
Visceral disease (liver and/or lung)	Excluded from study	Excluded from study	11%	13%

BPI-SF Q3, Brief Pain Inventory–Short Form Question #3; ECOG-PS, Eastern Cooperative Oncology Group performance status; LDH, Lactate dehydrogenase; NR, Not reported; PSA, Prostate-specific antigen.

Table 3. Inputs for drug treatment cost calculation.

Treatment	Abiraterone acetate plus prednisone	Enzalutamide
Time point	Final analysis^14	Final analysis^16
Median treatment duration (months)	14^15^,^a	18^16^,^a
WAC per 30-day supply^b	$8007.17^d^,^e	$8847.98^g
Total drug cost per treatment duration^c	$112,100	$159,264
Median OS (months)	34.7^14	35.3^16
Median rPFS (months)	16.5^f^,^7	20.0^h^,^17
Median time to chemotherapy (months)	25.2^f^,^7	28.0^16

a Rounded up to a whole number of months to align with a payer perspective. Hence, the median treatment duration for AA + P of 13.8 months was rounded to 14 months, and the median treatment duration for ENZ of 17.5 months was rounded to 18 months.

b WAC published in Analysource/First Databank.

c Rounded to nearest dollar.

d Abiraterone acetate: WAC = $7996.32 per 30-day supply; effective date: May 6, 2015.

e Prednisone: WAC = $0.1809 per 5-mg tablet; $10.85 per 60-count (30-day supply) 5-mg tablets; effective date: July 12, 2013.

f The analysis of radiographic progression-free survival requiring 378 events in the COU-AA-302 trial was fully matured at the time of the interim analyses.

g Enzalutamide: WAC = $8447.98 per 30-day supply; effective date: 4 February 2015.

h As the median time to rPFS at the initial analysis performed at 439 events, an extended rPFS analysis was conducted at 929 events.

OS, Overall survival; rPFS, radiographic progression-free survival; WAC, Wholesale acquisition cost.

Table 4. Treatment-related monitoring cost assumptions.^a

Monitoring recommendation^15	Test	Monitoring requirement	Average service payment^b	Number of tests during treatment	Cost for treatment duration	Monitoring cost per median OS month
Monitoring patients for hypertension, hypokalemia, and fluid retention at least once per month after starting AA + P. Control hypertension and correct hypokalemia before and during treatment with AA + P	Blood pressure measurement	Blood pressure measurement and fluid retention^c	$98.69	15^f	$1480.35	$42.66
	Observation for fluid retention
	Serum electrolyte test	Serum electrolyte test^d	$20.77	15^f	$311.55	$8.98
Monitor for signs and symptoms of adrenocortical insufficiency	Abnormal serum electrolyte test	Same test as row above
Measure serum transaminases (ALT and AST) and bilirubin before starting AA + P and every 2 weeks for the first 3 months after starting AA + P and monthly thereafter	Hepatic function panel consisting of ALT, AST, and bilirubin	Hepatic function panel^e	$26.80	18^g	$482.40	$13.90
Total monitoring costs					$2274.30	$65.54

a Based on recommendations in the prescribing information for abiraterone acetate¹⁵. The prescribing information for enzalutamide recommends monitoring in patients who may be treated concomitantly with warfarin, but it was not considered in this analysis¹⁶.

b Based upon the average payment (insurance + patient payment) for service in Truven Marketscan Commercial Claims and Encounters and Medicare Supplemental Data. Claims with a payment >$0 and <97.5th percentile were included in calculation of mean payment.

c Cost based upon average prolonged service code payment for CPT codes (99354–99356) in a specialty setting.

d Cost based upon electrolyte panel (CPT 80051).

e Cost based upon hepatic panel (CPT 80076) plus cost of SGOT test (CPT 84450).

f Assumes one test at baseline and one per month for 14 months based upon median treatment duration.

g Assumes one test at baseline and two per month for first 3 months (7 total), then one per month for 11 months, for a total of 18 tests over median treatment duration.

AA + P, Abiraterone acetate plus prednisone; OS, Overall survival.

Figure 1. Estimated cost per median overall survival month in chemotherapy-naïve mCRPC patients with mCRPC treated with abiraterone acetate plus prednisone or enzalutamide. AA + P, Abiraterone acetate plus prednisone; ENZ, enzalutamide.

Figure 2. Sensitivity analyses of estimated cost per median overall survival month in chemotherapy-naïve patients with mCRPC treated with abiraterone acetate plus prednisone or enzalutamide. AA + P, Abiraterone acetate plus prednisone; ENZ, enzalutamide.

Figure 3. Sensitivity analyses of estimated cost per median month of chemotherapy avoided and per median radiographic progression-free survival month in chemotherapy-naïve patients with mCRPC treated with abiraterone acetate plus prednisone or enzalutamide. AA + P, Abiraterone acetate plus prednisone; ENZ, enzalutamide; rPFS, radiographic progression-free survival.

Ryan CJ, Smith MR, de Bono JS, et al. Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med 2013; 368:138-48

 PubMed Web of Science ®Google Scholar

Beer TM, Armstrong AJ, Rathkopf DE, et al. Enzalutamide in metastatic prostate cancer before chemotherapy. N Engl J Med 2014;371:424-33

 PubMed Web of Science ®Google Scholar

Rathkopf DE, Smith MR, de Bono JS, et al. Updated interim efficacy analysis and long-term safety of abiraterone acetate in metastatic castration-resistant prostate cancer patients without prior chemotherapy (COU-AA-302). Eur Urol 2014;66:815-25

 PubMed Web of Science ®Google Scholar

Ryan CJ, Smith MR, Fizazi K, et al. Abiraterone acetate plus prednisone versus placebo plus prednisone in chemotherapy-naive men with metastatic castration-resistant prostate cancer (COU-AA-302): final overall survival analysis of a randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol 2015;16:152-60

 PubMed Web of Science ®Google Scholar

XTANDI® [package insert]. Northbrook, IL: Astellas Pharma US, Inc., 2015

 Google Scholar

ZYTIGA® [package insert]. Hornsham, PA: Janssen Biotech, Inc., 2015

 Google Scholar

Beer TM, Sternberg CN, Higano CS, et al. Enzalutamide (ENZA) in men with chemotherapy-Naïve metastatic castration-resistant prostate cancer (mCRPC): final analysis of the phase 3 PREVAIL study. Poster presented at the 2015 ASCO Annual Meeting, Chicago, IL

 Google Scholar