Real-world economic burden of metastatic castration-resistant prostate cancer before and after first-line therapy initiation

Figures & data

Figure 1. Study design scheme.

1L: first-line; HRU: Healthcare resource utilization; LOT: line of therapy; mCRPC: metastatic castration-resistant prostate cancer.

Figure 2. Patient identification flowchart.

1L: first-line; ARSIs: androgen receptor signaling inhibitors; EMR: electronic medical records; LOT: line of therapy; mCRPC: metastatic castration-resistant prostate cancer; PARP: poly ADP-ribose polymerase; PC: prostate cancer.

Note:

1. Medications considered for 1L mCRPC therapy were: ARSIs (i.e. apalutamide, darolutamide, enzalutamide, abiraterone acetate), chemotherapy (i.e. cabazitaxel, carboplatin, cisplatin, docetaxel, etoposide, mitoxantrone), PARP inhibitors (i.e. niraparib, olaparib, rucaparib, talazoparib), immunotherapy (i.e. sipuleucel-T, pembrolizumab), estrogens (i.e. estramustine phosphate, diethystillbestrol, polyestradiol phosphate), radiopharmaceuticals (i.e. radium-223, lutetium-177-PSMA-617).

Table 1. Baseline characteristics.

	mCRPC N = 459
Age at index date, mean ± SD [median]	70.0 ± 9.3 [70.0]
Race, n (%)
White	262 (57.1)
Black	71 (15.5)
Other	87 (19.0)
Unknown	31 (6.8)
Insurance plan type, n (%)
Commercial	206 (44.9)
Medicare Advantage	199 (43.4)
Medicaid	54 (11.8)
Practice type, n (%)
Community	426 (92.8)
Academic	29 (6.3)
Both	4 (0.9)
Stage at initial PC diagnosis, n (%)
Localized PC	241 (52.5)
mCSPC	218 (47.5)
Disease stage directly preceding mCRPC diagnosis, n (%)
mCSPC	364 (79.3)
nmCRPC	91 (19.8)
Localized PC	4 (0.9)
Year of index date, n (%)
2017	116 (25.3)
2018	106 (23.1)
2019	78 (17.0)
2020	94 (20.5)
2021	65 (14.2)
Time from PC diagnosis to 1 L therapy initiation, months, mean ± SD [median]	63.8 ± 72.3 [31.0]
Time from mCRPC diagnosis to 1 L therapy initiation, months, mean ± SD [median]	3.8 ± 6.6 [1.2]
Most recent ECOG performance score,^1,2 n (%)	349 (76.0)
0	159 (45.6)
1	151 (43.3)
2	31 (8.9)
3	7 (2.0)
4	1 (0.3)
Gleason score at initial PC diagnosis, n (%)
≤6	27 (5.9)
7	84 (18.3)
8	80 (17.4)
9	134 (29.2)
10	32 (7.0)
Not available	102 (22.2)
Prior evidence of ADT use,^3 n (%)	429 (93.5)
ADT monotherapy,^4,5 n (%)	171 (39.8)
Prior anti-androgen use,^4 n (%)	331 (72.1)
First-generation anti-androgens	145 (31.6)
ARSIs	257 (56.0)
Abiraterone acetate	157 (34.2)
Enzalutamide	116 (25.3)
Apalutamide	20 (4.4)
Darolutamide	5 (1.1)
Prior chemotherapy use,^4 (%)	41 (8.9)
Visceral metastasis,^6 n (%)	74 (16.1)
Quan-Charlson comorbidity index,^7 mean ± SD [median]	9.1 ± 3.1 [9.0]

1L: first-line; ADT: androgen deprivation therapy; ARSI: androgen receptor signaling inhibitors; ECOG: Eastern Cooperative Oncology Group; mCRPC: metastatic castration-resistant prostate cancer; mCSPC: metastatic castration-sensitive prostate cancer; nmCRPC: non-metastatic castration-resistant prostate cancer; PC: prostate cancer; SD: standard deviation.

Notes:

^1. ECOG scores were considered at any time prior to and including the index date.

^2. ECOG scores were defined as follows: 0 - Fully active; no performance restrictions; 1 - Strenuous physical activity restricted; fully ambulatory and able to carry out light work; 2 - Capable of all self-care but unable to carry out any work activities. Up and about >50% of waking hours; 3 - Capable of only limited self-care; confined to bed or chair >50% of waking hours; 4 - Completely disabled; cannot carry out any self-care; totally confined to bed or chair.

^3. Prior evidence of ADT use was defined as any ADT at any time prior to (and excluding) the index date.

^4. Evaluated in the 12-month baseline period.

^5. Defined as ADT use without use of ARSIs, chemotherapy, PARP inhibitors, immunotherapy, estrogens, or radiopharmaceuticals.

^6. Visceral metastasis was assessed any time prior to and including the index date.

^7. Quan H, Li B, Couris CM, et al. Updating and validating the Charlson comorbidity index and score for risk adjustment in hospital discharge abstracts using data from 6 countries. Am J Epidemiol. 2011;173(6):676-682.

Table 2. Baseline and follow-up HRU¹ PPPM.

Mean ± SD [median] or n (%)		Baseline		Follow-up
	Overall	Pre-mCRPC	Post-mCRPC	Overall	1L	2L	3L
	N = 459	N = 416	N = 400	N = 459	N = 459	N = 166	N = 86
Length of period, months	12.0 ± 0.0 [12.0]	10.0 ± 2.4 [10.9]	3.3 ± 3.8 [3.3]	15.2 ± 11.8 [12.3]	8.5 ± 8.2 [5.6]	6.5 ± 5.7 [5.1]	5.2 ± 4.9 [3.2]
<30 days	–	2 (0.5)	141 (35.3)	12 (2.6)	27 (5.9)	7 (4.2)	10 (11.6)
All-cause
Inpatient admissions
≥1 inpatient admission	189 (41.2)	155 (37.3)	67 (16.8)	281 (61.2)	160 (34.9)	63 (38.0)	32 (37.2)
No. of admissions	0.11 ± 0.24 [0.00]	0.11 ± 0.25 [0.00]	0.15 ± 0.49 [0.00]	0.26 ± 0.80 [0.09]	0.15 ± 0.36 [0.00]	0.21 ± 0.50 [0.00]	0.17 ± 0.32 [0.00]
No. of days	1.18 ± 3.45 [0.00]	1.18 ± 3.72 [0.00]	1.57 ± 5.19 [0.00]	2.83 ± 5.37 [0.46]	2.05 ± 5.35 [0.00]	2.53 ± 6.22 [0.00]	2.00 ± 5.02 [0.00]
No. of days per admission	9.73 ± 13.61 [6.00]	9.00 ± 11.54 [5.50]	11.28 ± 12.83 [8.00]	12.75 ± 26.22 [7.50]	11.31 ± 14.83 [6.42]	13.20 ± 26.86 [5.00]	10.84 ± 11.03 [5.00]
Emergency room visits
≥1 emergency room visit	178 (38.8)	142 (34.1)	59 (14.8)	196 (42.7)	124 (27.0)	49 (29.5)	17 (19.8)
No. of days with visits	0.07 ± 0.17 [0.00]	0.07 ± 0.18 [0.00]	0.17 ± 1.56 [0.00]	0.10 ± 0.25 [0.00]	0.09 ± 0.28 [0.00]	0.10 ± 0.26 [0.00]	0.07 ± 0.25 [0.00]
Outpatient visits
≥1 outpatient visit	455 (99.1)	408 (98.1)	378 (94.5)	451 (98.3)	450 (98.0)	161 (97.0)	86 (100.0)
No. of days with visits	2.68 ± 2.21 [2.26]	2.56 ± 2.28 [2.24]	4.94 ± 5.42 [3.72]	3.38 ± 2.97 [2.88]	3.75 ± 3.63 [2.88]	3.94 ± 2.57 [3.34]	5.33 ± 4.98 [3.91]
Pharmacy claims
≥1 pharmacy claims	443 (96.5)	391 (94.0)	340 (85.0)	447 (97.4)	443 (96.5)	162 (97.6)	82 (95.3)
No. of pharmacy claims	3.25 ± 2.92 [2.42]	3.20 ± 2.96 [2.42]	4.84 ± 10.95 [2.90]	4.22 ± 3.28 [3.37]	4.44 ± 3.77 [3.59]	4.65 ± 2.88 [4.02]	5.33 ± 7.02 [3.84]
Other services
≥1 other service	22 (4.8)	18 (4.3)	8 (2.0)	20 (4.4)	16 (3.5)	6 (3.6)	3 (3.5)
No. of days with other services	0.03 ± 0.28 [0.00]	0.03 ± 0.28 [0.00]	0.05 ± 0.57 [0.00]	0.05 ± 0.60 [0.00]	0.06 ± 0.63 [0.00]	0.03 ± 0.23 [0.00]	0.05 ± 0.38 [0.00]
PC-related^2
Inpatient admissions
≥1 inpatient admission	165 (35.9)	131 (31.5)	62 (15.5)	259 (56.4)	144 (31.4)	60 (36.1)	32 (37.2)
No. of admissions	0.08 ± 0.17 [0.00]	0.07 ± 0.17 [0.00]	0.13 ± 0.46 [0.00]	0.22 ± 0.78 [0.06]	0.12 ± 0.29 [0.00]	0.19 ± 0.47 [0.00]	0.16 ± 0.32 [0.00]
No. of days	0.98 ± 2.87 [0.00]	0.96 ± 3.08 [0.00]	1.49 ± 5.09 [0.00]	2.57 ± 5.07 [0.25]	1.87 ± 5.04 [0.00]	2.46 ± 6.13 [0.00]	1.98 ± 4.99 [0.00]
No. of days per admission	11.64 ± 15.00 [6.67]	11.08 ± 13.00 [6.00]	12.69 ± 14.22 [8.50]	13.88 ± 27.52 [8.50]	12.80 ± 16.16 [8.00]	14.22 ± 27.67 [5.33]	12.04 ± 15.31 [5.00]
Emergency room visits
≥1 emergency room visit	70 (15.3)	48 (11.5)	32 (8.0)	96 (20.9)	54 (11.8)	20 (12.0)	7 (8.1)
No. of days with visits	0.02 ± 0.08 [0.00]	0.02 ± 0.08 [0.00]	0.09 ± 0.83 [0.00]	0.04 ± 0.17 [0.00]	0.04 ± 0.21 [0.00]	0.03 ± 0.16 [0.00]	0.02 ± 0.09 [0.00]
Outpatient visits
≥1 outpatient visit	449 (97.8)	401 (96.4)	367 (91.8)	441 (96.1)	439 (95.6)	160 (96.4)	86 (100.0)
No. of days with visits	1.49 ± 0.96 [1.34]	1.34 ± 1.00 [1.14]	3.67 ± 4.59 [2.47]	2.35 ± 2.23 [1.87]	2.62 ± 2.84 [1.98]	2.91 ± 1.83 [2.61]	4.49 ± 4.93 [3.13]
Pharmacy claims
≥1 pharmacy claims	303 (66.0)	245 (58.9)	166 (41.5)	373 (81.3)	350 (76.3)	107 (64.5)	33 (38.4)
No. of pharmacy claims	0.37 ± 0.45 [0.17]	0.36 ± 0.46 [0.12]	0.67 ± 2.45 [0.00]	0.61 ± 0.58 [0.51]	0.77 ± 0.70 [0.80]	0.62 ± 0.67 [0.56]	0.35 ± 0.55 [0.00]
Other services
≥1 other service	1 (0.2)	1 (0.2)	0 (0.0)	4 (0.9)	2 (0.4)	1 (0.6)	3 (3.5)
No. of days with other services	0.00 ± 0.00 [0.00]	0.00 ± 0.00 [0.00]	0.00 ± 0.00 [0.00]	0.00 ± 0.07 [0.00]	0.00 ± 0.03 [0.00]	0.02 ± 0.22 [0.00]	0.05 ± 0.37 [0.00]

1L: first-line; 2 L: second-line; 3 L: third-line; ARSI: androgen receptor signaling inhibitors; HRU: Healthcare resource utilization; ICD-10-CM: International Classification of Diseases 10th Revision Clinical Modification; LHRH: luteinizing hormone-releasing hormone; mCRPC: metastatic castration-resistant prostate cancer; No.: number; PARP: poly ADP-ribose polymerase; PC: prostate cancer; PPPM: per-patient-per-month; SD: standard deviation.

Notes:

^1. All-cause and PC-related HRU were identified based on medical claims and the number of days with all-cause or PC-related pharmacy claims were identified based on dates with a dispensed medication (i.e. a filled pharmacy claim).

^2. PC-related HRU and costs were identified with the ICD-10-CM code C61 and procedure codes for LHRH or of the following guideline-recommended therapies for mCRPC: androgen ARSIs, chemotherapy, PARP inhibitors, immunotherapy, estrogens, and radiopharmaceuticals.

Figure 4. Regimens used as Flatiron oncologist-defined 1 L, 2 L, and 3 L mCRPC therapy^1,2.

1L: first-line; 2L: second-line; 3L: third-line; ARSI: androgen receptor signaling inhibitor; Chemo: chemotherapy; mCRPC: metastatic castration-resistant prostate cancer.

Notes:

1. All individual agents reported were used as monotherapy in Flatiron oncologist-defined 1L, 2L, or 3L mCRPC therapy.

2. Medications considered for other monotherapy were: ARSIs (i.e. darolutamide), chemotherapy (i.e. cisplatin, mitoxantrone), PARP inhibitors (i.e. olaparib), and immunotherapy (i.e. pembrolizumab).

3. Among 164 patients treated with abiraterone acetate monotherapy as 1L, 54 (32.9%) had a claim for generic abiraterone acetate while 110 (67.1%) had a claim for branded abiraterone acetate (i.e. Zytiga [108] or Yonsa [2]) as their first claim on or after the date of mCRPC.

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Data availability statement

Data that support the findings of this study were used under license from Flatiron Health, Inc. and Komodo Health Solutions. Restrictions apply to the availability of these data, which are not publicly available and cannot be shared. The data are available through request made directly to the data vendor, subject to the data vendor’s requirements for data access.