Real-World Outcomes of Second Novel Hormonal Therapy or Radium-223 Following First Novel Hormonal Therapy for mCRPC

Figures & data

Figure 1. CONSORT flow diagram.

mCRPC: Metastatic castration-resistant prostate cancer; NHT: Novel hormonal therapy.

Table 1. Patient demographics and disease characteristics.

Characteristic^†	After first-line NHT
	Second-line radium-223 (n = 120)	Second-line alternative NHT (n = 226)
At initial diagnosis
Gleason score, n (%) – >7 – ≤7 – Unknown/not documented	56 (47) 33 (28) 31 (26)	102 (45) 56 (25) 68 (30)
Metastatic stage, n (%) – M0 – M1 – Unknown/not documented	44 (37) 47 (39) 29 (24)	70 (31) 83 (37) 73 (32)
Race, n (%) – White – Black or African American – Asian – Other – Missing	91 (76) 8 (7) 1 (1) 12 (10) 8 (7)	145 (64) 26 (12) 7 (3) 36 (16) 12 (5)
At the start of second-line therapy
Median age, years (range)	75 (50–84)	79 (51–84)
ECOG performance status, n (%) – 0 or 1 – ≥2 – Missing	59 (49) 17 (14) 44 (37)	101 (45) 40 (18) 85 (37)
Site of metastasis, n (%) – Bone only – Distant lymph node ± bone – Visceral ± bone or lymph node – Missing	92 (77) 13 (11) 15 (13) 0	127 (56) 50 (22) 47 (21) 2 (1)
Prior SSEs, n (%)	61 (51)	75 (33)
Prior treatment with a BHA, n (%)	68 (57)	130 (58)
Prior chemotherapy (docetaxel or cabazitaxel) for mHSPC, n (%)	15 (13)	14 (6)
Median laboratory values – ALP, U/l – Hemoglobin, g/dl – LDH, U/l – Prostate-specific antigen, μg/l	105 (n = 97) 12 (n = 97) 226 (n = 18) 48 (n = 90)	106 (n = 194) 12 (n = 196) 215 (n = 46) 34 (n = 187)
Hemoglobin, n (%) – ≤12.8 g/dl – >12.8 g/dl – Missing	72 (60) 25 (21) 23 (19)	146 (65) 50 (22) 30 (13)
Median duration of first-line NHT, months	6.0	7.5
Median time from diagnosis of mCRPC to start of second-line therapy, months	9.7	9.9

† Unless otherwise specified, data were recorded at the start of second-line therapy.

BHA: Bone health agent; ECOG: Eastern Cooperative Oncology Group; mCRPC: Metastatic castration-resistant prostate cancer; mHSPC: Metastatic hormone-sensitive prostate cancer; NHT: Novel hormonal therapy; SSE: Symptomatic skeletal event.

Table 2. Subsequent life-prolonging therapy after second-line therapy.

Subsequent therapy	After first-line NHT
	Second-line radium-223 (n = 120)	Second-line alternative NHT (n = 226)
Any subsequent life-prolonging therapy, n (%) – 1 line – 2 lines – 3 lines – >3 lines	59 (49) 36 (30) 15 (13) 6 (5) 2 (2)	88 (39) 53 (23) 22 (10) 9 (4) 4 (2)
Third-line life-prolonging therapy, n/N^† (%) – NHT – Taxane – NHT + taxane – NHT + other treatment – Taxane + other treatment – Other treatment	30/59 (51) 16/59 (27) 0 7/59 (12) 0 6/59 (10)	15/88 (17) 56/88 (64) 4/88 (5) 4/88 (5) 1/88 (1) 8/88 (9)
Fourth-line life-prolonging therapy, n/N^† (%) – NHT – Taxane – NHT + taxane – NHT + other treatment – Taxane + other treatment – Other treatment	5/59 (8) 13/59 (22) 0 2/59 (3) 0 3/59 (5)	5/88 (6) 22/88 (25) 3/88 (3) 1/88 (1) 1/88 (1) 3/88 (3)
Subsequent chemotherapy, n/N^† (%) – Docetaxel and/or cabazitaxel – Docetaxel and cabazitaxel – Other chemotherapy	28/59 (47) 6/59 (10) 1/59 (2)	67/88 (76) 26/88 (30) 4/88 (5)

† The denominator (n) is all patients who received subsequent therapy in each cohort.

NHT: Novel hormonal therapy.

Figure 2. Subsequent life-prolonging therapy after second-line therapy.

^†Patients were counted once for each treatment type, regardless of the number of lines received; patients who received more than one treatment type were counted in each category.

^‡The denominator is the number of patients in each cohort who received any subsequent therapy (radium-223 n = 59; alternative NHT n = 88).

^§In the radium-223 cohort, one patient received subsequent radium-223 monotherapy; in the alternative NHT cohort, one patient received subsequent pembrolizumab monotherapy, and one patient received subsequent sipuleucel-T monotherapy.

NHT: Novel hormonal therapy.

Table 3. Multivariable Cox proportional hazards regression model for time to first use of subsequent taxane therapy^†, ‡.

Parameter^§	Hazard ratio	95% CI	p-value
Study cohort (second-line radium-223 vs alternative NHT)	0.66	0.39–1.12	0.1240
Age (years)	0.96	0.93–0.98	0.0010
Hemoglobin (>12.8 vs ≤12.8 g/dl)	0.56	0.33–0.95	0.0323

† Analysis included patients without missing values: radium-223 cohort 87 patients, 20 subsequent taxane events; alternative NHT cohort 177 patients, 54 subsequent taxane events.

‡ Initial model included age, race, Eastern Cooperative Oncology Group performance status, Gleason score, site of metastasis, prior use of bone health agents, prior symptomatic skeletal events, prior chemotherapy, hemoglobin, log-transformed prostate-specific antigen and log-transformed ALP.

§ Perameter (recorded at the start of second-line radium-223 or second-line alternative NHT) predicting the time to first use of subsequent taxane therapy.

NHT: Novel hormonal therapy.

Table 4. Multivariable cox proportional hazards regression model for symptomatic skeletal event occurrence^†, ‡.

Parameter^§	Hazard ratio	95% CI	p-value
Study cohort (second-line radium-223 vs alternative NHT)	0.66	0.37–1.17	0.1524
Age (years)	0.95	0.92–0.98	0.0014
Prior BHA use (yes vs no)	0.49	0.29–0.82	0.0071
Prior SSE (yes vs no)	2.51	1.48–4.26	0.0006

† Analysis included patients without missing values: radium-223 cohort 87 patients, 19 SSEs; alternative NHT cohort 177 patients, 42 SSEs.

‡ Initial model included age, race, Eastern Cooperative Oncology Group performance status, Gleason score, site of metastasis, prior use of BHAs, prior SSEs, prior chemotherapy, hemoglobin, log-transformed prostate-specific antigen, and log-transformed ALP.

§ Parameter (recorded at the start of second-line radium-223 or second-line alternative NHT) predicting the future occurrence of SSEs.

BHA: Bone health agent; NHT: Novel hormonal therapy; SSE: Symptomatic skeletal event.

Figure 3. Kaplan–Meier estimates of OS from the start of second-line therapy.

(A) Radium-223 cohort. (B) Alternative NHT cohort.

NHT: Novel hormonal therapy; OS: Overall survival.

Table 5. Multivariable Cox proportional hazards regression model for overall survival^†, ‡.

Parameter^§	Hazard ratio	95% CI	p-value
Cohort (second-line radium-223 vs alternative NHT)	1.26	0.92–1.74	0.1552
Site of metastasis (lymph node ± bone vs bone only)	1.13	0.74–1.72	0.5702
Site of metastasis (visceral ± lymph node/bone vs bone only)	1.69	1.17–2.42	0.0048
Hemoglobin (>12.8 vs ≤12.8 g/dl)	0.58	0.40–0.84	0.0038
Log-transformed PSA (μg/l)	1.19	1.07–1.32	0.0019
Log-transformed ALP (U/l)	1.41	1.14–1.76	0.0019

† Analysis included patients without missing values: radium-223 cohort 87 patients, 65 death events; alternative NHT cohort 177 patients, 124 death events.

‡ Initial model included age, race, Eastern Cooperative Oncology Group performance status, Gleason score, site of metastasis, prior use of bone health agents, prior symptomatic skeletal events, prior chemotherapy, hemoglobin, log-transformed PSA, and log-transformed ALP.

§ Parameter (recorded at the start of second-line radium-223 or second-line alternative NHT) predicting overall survival.

NHT: Novel hormonal therapy; PSA: Prostate-specific antigen.