Real-world evaluation of upfront docetaxel in metastatic castration-sensitive prostate cancer

Table 1 Baseline characteristics of the first 94 patients with metastatic castration-sensitive prostate cancer treated with docetaxel and androgen deprivation therapy between July 2015 and December 2017 in the Southeast Health Care region of Sweden

	Total, n = 94 (%)	CHAARTED, ADT + Docetaxel	STAMPEDE, Standard of care + Docetaxel
Age, yr
Median	68.0	64	65
Range	49-79	36-88	40-81
Prostate-specific antigen (μg/L), at diagnosis
Median	180	50.9	70
Range	2-7367	0.2-8540.1	1-9999
Comorbidities, n (%)	50 (53)
Diabetes mellitus I and II	16 (17)		56 (9)
Hyperlipidemia	23 (24)		208 (35)
Hypertension	38 (40)
Previous malignant disease1	11 (11)
Performance status (ECOG)2, n (%)
0	46 (72)	277 (69.8)
1	15 (23)	114 (28.7)
2	3 (5)	6 (1.5)
T category at diagnosis3, n (%)
T1	6 (6)		0
T2	17 (18)		60 (10)
T3	46 (49)		390 (66)
T4	11 (12)		105 (18)
TX	4 (4)		35 (6)
Not assessed	10 (11)
N category at diagnosis3, n (%)
N0	29 (31)		260 (44)
N1	42 (45)		298 (50)
NX	23 (24)		34 (6)
Metastases3, n (%)
Non-distant metastasis4	19 (20)
Distant metastases	75 (80)		362 (61)
Location, n (%)
Bone metastases	74 (79)		307 (52)
Liver metastases	2 (2)		6 (1)
Lung metastases	12 (13)		13 (2)
Lymph node metastases	54 (57)		102 (17)
Gleason sum score, n (%)
≤ 6	2 (2)	21 (5.3)	≤ 7
7	27 (29)	96 (24.2)	110 (19%)
8-10	60 (64)	241 (60.7)	436 (74%)
Unknown	5 (5)	39 (9.8)	46 (8%)
Histology (WHO 2004), n (%)
Acinar adenocarcinoma	86 (92)
Ductal carcinoma	1 (1)
Mixed type	2 (2)
Unknown	5 (5)
Follow-up, months	20
Median (IQR)	13-28
Status last follow-up, n (%)
Alive, no disease progression	15 (16)
Alive, disease progression	65 (69)
Dead of disease	14 (15)

¹Previous non-prostate cancer: Not specified (n = 6), basal cell carcinoma (n = 1), malignant melanoma (n = 2), pancreatic cancer (n = 1), thyroid cancer (n = 1).

²ECOG: Eastern Cooperative Oncology Group performance status. This information was available for 64 of 94 patients (68%).

³Staging according to TNM classification (8^th edition UICC 2017); clinical staging n = 85, pathological staging n = 7. No information was found for n = 2. X means that a substage was not defined.

⁴Locoregional lymph node metastases are referred to as non-distant metastases. Corresponding data from the CHAARTED and STAMPEDE randomized trials[10,11] are shown for comparison.

ADT: Androgen deprivation therapy; PFS: Progression-free survival.

Table 2 Treatment data

	Total, n = 94 (%)
ADT
GnRH and nonsteroidal antiandrogen	82 (87)
GnRH alone	9 (10)
Orchidectomy	3 (3)
ADT
Time from ADT start to Docetaxel start, days
Median (range)	63 (8-400)
ADT duration, days
Median (range)	331 (5-1038)
Docetaxel
751 mg/m²	77
Adm mean dose % of full dose	91
Mean adm dose, mg	139
Mean acc dose, mg	758
Completed all cycles	63 (67)
502 mg/m²	8
Adm mean dose % of full dose	83
Mean adm dose, mg	86
Mean acc dose, mg	610
Completed all cycles	4 (50)
Switch	9
Adm mean dose % of full dose	87
Mean adm dose, mg	107
Mean acc dose, mg	641
Completed all cycles	9 (100)
Dose reduction	33 (35)
Dose escalation	13 (14)
Unchanged	47 (50)
Missing	1 (1)
Best response at end of Docetaxel3
CR	6 (6)
PR	50 (53)
SD	15 (16)
PD	11 (12)
NE	12 (13)
Est. PFS	Mean (95%CI)
12 mo
CHAARTED/STAMPEDE	75% (66-84)
Swedish national guidelines	71% (61-81)
24 mo
CHAARTED/STAMPEDE	58% (46-70)
Swedish national guidelines	55% (43-67)
OS
12 mo	93% (87-99)
24 mo	86% (76-96)

¹75 mg/m² is given in 6 cycles every 21 d.

²50 mg/m² is given in 9 cycles every 14 d.

³CR: Complete response; PR: Partial response; SD: Stable disease; PD: Progressive disease. (PD definition CHAARTED: Serologic increase of PSA level of more than 50% above nadir reached after initiation of androgen deprivation therapy, two consecutive increases at least 2 wk apart. If the nadir was less than 2 μg/L, a minimum increase of more than 2 μg/L was required. STAMPEDE: Biochemical progression rose by 50% above the within 24-wk nadir and above 4 μg/L. Radiologic according to RECIST version 1.0 Swedish national guidelines: Clinical: Increasing symptoms or deterioration of general condition. Serologic ≥ 25 percent from lowest PSA value after start of latest given treatment an augmentation of at least ≥ 2 μg/L is required. Radiologic progression of existing or new metastasis).

NE: Nonevaluable; ADT: Androgen deprivation therapy; PFS: Progression-free survival.

Table 3 Progression-free survival (according to the CHAARTED and STAMPEDE definitions of progressive disease) age, PSA, comorbidities and bone metastases

	Number of patients	Number of events	HR, 95%CI, P value (univariate)	HR, 95%CI, P value (multivariate)
Age, yr (median)
≤ 68	48	21	1.00	1.00
> 68	46	15	0.78, 0.40-1.51, 0.45	0.83, 0.42-1.67, 0.61
PSA (median)
≤ 180	48	12	1.00	1.00
> 180	46	24	2.86, 1.39-5.87, 0.0041	2.51, 1.21-5.19, 0.013
Comorbidities
No	44	15	1.00	1.00
Yes	50	21	1.15, 0.59-2.23, 0.68	1.19, 0.60-2.36, 0.63
Distant metastases
No	19	3	1.00	1.00
Yes	75	33	3.36, 1.03-10.96, 0.045	2.60, 0.78-8.65, 0.12

Table 4 Progression-free survival (according to Swedish national guidelines) age, PSA, comorbidities and bone metastases

	Number of patients	Number of events	HR, 95%CI, P value (univariate)	HR, 95%CI, P value (multivariate)
Age, yr (median)
≤ 68	48	22	1.00	1.00
> 68	46	17	0.83, 0.44-1.56, 0.55	0.88, 0.46-1.71, 0.71
PSA (median)
≤ 180	48	13	1.00	1.00
> 180	46	26	2.86, 1.44-5.69, 0.0028	2.57, 1.28-5.16, 0.0081
Comorbidities
No	44	17	1.00	1.00
Yes	50	22	1.06, 0.56-2.00, 0.85	1.08, 0.56-2.07, 0.83
Distant metastases
No	19	4	1.00	1.00
Yes	75	35	2.69, 0.96-7.59, 0.061	2.11, 0.73-6.06, 0.17

Table 5 Side-effects reported

	Total, n = 94 (%)
Reason for termination of treatment
Completed as planned	74 (79)
Adverse event	11 (12)
Fatigue	5 (5)
Tumor progression	2 (2)
Patient preference	1 (1)
Other	1 (1)
Bone marrow toxicity
Hemoglobin
Any grade	16 (17)
≥ grade 3-4	0
White blood cell count
Any grade	20 (21)
≥ grade 3-4	15 (16)
Neutrophil count
Any grade	19 (20)
≥ grade 3-4	19 (20)
Grade missing	1
Platelet count
Any grade	2 (2)
≥ grade 3-4	0
Unplanned hospitalization under and within 30 d after chemotherapy	24 (26)
Febrile neutropenia	20 (21)