Darolutamide in Spanish patients with nonmetastatic castration-resistant prostate cancer: ARAMIS subgroup analysis

Figures & data

Table 1. Baseline patient demographics and clinical characteristics of the ARAMIS Spanish subgroup and overall population.

Characteristic	Spanish subgroup		All patients
	Darolutamide (n = 75)	Placebo (n = 42)	Darolutamide (n = 955)	Placebo (n = 554)
Age, median (range, years)	76 (52–89)	75 (54–90)	74 (48–95)	74 (50–92)
ECOG PS, n (%)
0	64 (85)	36 (86)	650 (68)	391 (71)
1	11 (15)	6 (14)	305 (32)	163 (29)
Gleason score ≥7, n (%)	60 (80)	28 (67)	711 (74)	395 (71)
Time from initial diagnosis, median (range, months)	112.2 (2.6–249.1)	111.1 (3.2–236.7)	86.2 (2.6–337.5)	84.2 (0.5–344.7)
Presence of lymph nodes on central imaging review, n (%)	10 (13)	11 (26)	100 (10)	66 (12)
Serum PSA level, median (range, ng/ml)	12.8 (2.3–130.5)	18.4 (4.5–108.7)	9.0 (0.3–858.3)	9.7 (1.5–885.2)
PSADT
Median (range, months)	4.8 (1.1–9.9)	5.3 (1.1–10.2)	4.4 (0.7–11.0)	4.7 (0.7–13.2)
≤6 months, n (%)	53 (71)	25 (60)	667 (70)	371 (67)
>6 months, n (%)	22 (29)	17 (40)	288 (30)	183 (33)
Serum testosterone level, median (range, nmol/l)	0.6 (0.3–1.3)	0.6 (0.2–1.6)	0.6 (0.2–25.9)	0.6 (0.2–7.3)
Use of bone-sparing agent, n (%)	2 (3)	2 (5)	31 (3)	32 (6)
≥1 prior hormonal therapy, n (%)	73 (97)	41 (98)	904 (95)	523 (94)

ECOG PS: Eastern Cooperative Oncology Group performance status; PSA: Prostate-specific antigen; PSADT: Prostate-specific antigen doubling time.

Data for ‘All patients’ are from [10] Copyright © 2019 Massachusetts Medical Society. Reprinted with permission.

Figure 1. Kaplan-Meier estimates of MFS at the primary analysis (intention-to-treat population).

(A) Spanish subgroup; (B) overall population.

HR: Hazard ratio; MFS: Metastasis-free survival; NE: Not estimable; NR: Not reached.

Data for ‘All patients’ are from [10] Copyright © 2019 Massachusetts Medical Society. Reprinted with permission.

Figure 2. Kaplan-Meier estimates of time to PSA progression at the ARAMIS primary analysis (intention-to-treatpopulation).

(A) Spanish subgroup; (B) overall population.

HR: Hazard ratio; NE: Not estimable; PSA: Prostate-specific antigen.

Data for ‘All patients’ are from [10] Copyright © 2019 Massachusetts Medical Society. Reprinted with permission.

Table 2. Prostate-specific antigen response^† in the ARAMIS Spanish subgroup and overall population.

	Spanish subgroup		All patients
	Darolutamide (n = 75)	Placebo (n = 42)	Darolutamide (n = 955)	Placebo (n = 554)
Overall PSA response during study drug treatment n (%)	67 (89)	6 (14)	798 (84)	42 (8)
Difference (darolutamide vs placebo)	-75 (95% CI -88, -62)		-76 (95% CI -79, -73)
Maximal decline from baseline n (%)
No post-baseline value	2 (3)	0	55 (6)	24 (4)
No decline	3 (4)	29 (69)	34 (4)	383 (69)
≥0 and <30%	2 (3)	5 (12)	30 (3)	84 (15)
≥30 and <50%	1 (1)	2 (5)	38 (4)	21 (4)
≥50 and <90%	28 (37)	4 (10)	312 (33)	32 (6)
≥90%	39 (52)	2 (5)	486 (51)	10 (2)

† Defined as an ≥50% decrease in PSA level from baseline.

Difference in response rate calculated using the Cochran-Mantel-Haenszel test.

PSA: Prostate-specific antigen.

Table 3. Treatment-emergent adverse events in the ARAMIS Spanish subgroup and overall population (safety population).

n (%)	Spanish subgroup		All patients
	Darolutamide (n = 75)	Placebo (n = 42)	Darolutamide (n = 955^†)	Placebo (n = 554)
Any	67 (89)	38 (90)	818 (86)	439 (79)
Grade 1 or 2	45 (60)	30 (71)	521 (55)	300 (54)
Grade 3 or 4	16 (21)	8 (19)	251 (26)	120 (22)
Grade 5	6 (8)	0	38 (4)	19 (3)
Serious	18 (24)	8 (19)	237 (25)	111 (20)
Leading to dose modification	14 (19)	4 (10)	135 (14)	52 (9)
Leading to discontinuation	6 (8)	2 (5)	85 (9)	48 (9)
Drug-related	25 (33)	11 (26)	258 (27)	110 (20)
Adverse events of special interest
Fatigue/asthenic conditions	14 (19)	7 (17)	164 (17)	63 (11)
Fatigue	9 (12)	3 (7)	126 (13)	46 (8)
Asthenia	6 (8)	6 (14)	38 (4)	17 (3)
Bone fracture	3 (4)	2 (5)	52 (5)	20 (4)
Falls, including accident	1 (1)	3 (7)	50 (5)	27 (5)
Weight decrease	0	0	40 (4)	14 (3)
Seizure	1 (1)	0	2 (<1)	1 (<1)
Mental impairment disorder	1 (1)	1 (2)	19 (2)	10 (2)
Depressed-mood disorder	4 (5)	1 (2)	21 (2)	10 (2)
Rash	1 (1)	1 (2)	30 (3)	6 (1)
Hypertension	8 (11)	3 (7)	74 (8)	36 (6)
Hot flush	7 (9)	3 (7)	57 (6)	25 (5)
Cardiac arrhythmia	4 (5)	2 (5)	70 (7)	24 (4)
Coronary artery disorder	1 (1)	1 (2)	38 (4)	15 (3)
Heart failure	2 (3)	0	18 (2)	5 (1)

† One patient did not receive darolutamide and was not included in the safety analyses.

Data for ‘All patients’ are from [16] Copyright © 2020 Massachusetts Medical Society. Reprinted with permission.

Fizazi K , ShoreN, TammelaTLet al. Darolutamide in nonmetastatic, castration-resistant prostate cancer. N. Engl. J. Med.380(13), 1235–1246 (2019).

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Fizazi K , ShoreN, TammelaTLet al. Nonmetastatic, castration-resistant prostate cancer and survival with darolutamide. N. Engl. J. Med.383(11), 1040–1049 (2020).

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