Real-world comparison of cabazitaxel vs. 177-lutetium-PSMA radioligand therapy in metastatic castration resistant prostate cancer.
Authors: Wenzel Mike , Koll Florestan , Hoeh Benedikt , Humke Clara , Siech Carolin , Mader Nicolai , Groener Daniel , Steuber Thomas , Graefen Markus , Maurer Tobias , Brandts Christian H , Banek Severine , Chun Felix , Mandel Philipp 
Published: February 2025

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Background:
177-Lutetium Prostate-specific membrane antigen (Lu-PSMA) therapy is under current scientific investigation and aims to become an established part in treatment of metastatic castration resistant prostate cancer (mCRPC). However, real-world evidence in treatment comparison is scant.
Methods:
We relied on the FRAMCAP database and compared cabazitaxel vs. Lu-PSMA therapy in mCRPC patients regarding progression-free (PFS) and overall (OS). Sensitivity analyses addressed 2
nd
to 4
th
line mCRPC patients to approximate current Phase-III patient selection criteria.
Results:
Of 373 mCRPC patients, 14% received cabazitaxel vs. 65% Lu-PSMA vs. 21% both. Patients undergoing Lu-PSMA therapy were significantly older (median 72 vs. 66 years, p<0.01) and displayed a higher proportion of ECOG ≥2 (12 vs. 5.0%, p=0.1), relative to cabazitaxel patients. Rates of PSA50 were 32% vs. 0% for Lu-PSMA vs. cabazitaxel. In outcome analyses, significant superior median PFS was observed for Lu-PSMA vs. cabazitaxel (13.4 vs. 7.1 months, p<0.001), even after multivariable adjustment (HR: 0.38, p<0.001). Regarding OS, rates also significantly differed with median OS of 14.7 vs. 16.5 vs. 29.6 months for cabazitaxel vs. Lu-PSMA vs. both treatments (p<0.01). In sensitivity analyses of 2
nd
to 4
th
line mCRPC, PFS rates and median OS rates for cabazitaxel vs. Lu-PSMA vs. both therapies qualitatively remained the same compared to the entire cohort.
Conclusions:
In real-world setting, Lu-PSMA provides significantly better PFS and qualitatively better OS rates compared to cabazitaxel chemotherapy and should therefore be considered as a valuable treatment option for advanced mCRPC patients according to the EMA-approval.

Characteristics of 296 metastatic castration resistant prostate cancer (mCRPC) patients stratified according to treatment of cabazitaxel vs. 177
-
Lutetium- prostate-specific membrane antigen radioligand therapy (Lu-PSMA).

Characteristic
N

Overall,N = 296

1

CabazitaxelN = 52 (18%)

1

Lu-PSMA,N = 244 (82%)

1

p-value

2

Age at mCRPC, years
192
71 (64, 76)
66 (58, 71)
72 (66, 78)
<0.001

PSA at m CRPC, ng/ml
141
18 (6, 72)
63 (12, 144)
15 (6, 64)
0.044

Number of CRPC lines
296
3 (2, 4)
4 (3, 5)
3 (2, 4)
<0.001

Cycles systemic treatment
229
3 (2, 6)
5 (3, 6)
3 (2, 6)
0.031

PSA response, %
39
20 (0, 66)
15 (0, 23)
25 (0, 68)
0.3

PSA50
39
11 (28%)
0 (0%)
11 (32%)
0.3

PSA90
39
5 (13%)
0 (0%)
5 (15%)
0.9

ECOG status at mCRPC
109

0.10

0

52 (48%)
14 (70%)
38 (43%)

1

45 (41%)
5 (25%)
40 (45%)

>=2

12 (11%)
1 (5%)
11 (12%)

Cardiovascular disease
183
66 (36%)
13 (35%)
53 (36%)
0.9

Gleason Score 8-10
259
181 (70%)
39 (80%)
142 (68%)
0.10

De Novo mHSPC
290
161 (56%)
33 (63%)
128 (54%)
0.2

High volume mHSPC
146
99 (68%)
24 (73%)
75 (66%)
0.5

Metastatic sites at mCRPC
130

0.8

M1a

14 (11%)
3 (13%)
11 (10%)

M1b

104 (80%)
20 (83%)
84 (79%)

M1c

12 (9%)
1 (4%)
11 (10%)

Treatment mHSPC
126

0.034

ADT mono

25 (20%)
4 (20%)
21 (20%)

ARSI

58 (46%)
4 (20%)
54 (51%)

Docetaxel

34 (27%)
10 (50%)
24 (23%)

Triplet

3 (2%)
1 (5%)
2 (2%)

Other

6 (5%)
1 (5%)
5 (5%)

Treatment 1st line mCRPC
296

<0.001

ADT mono

29 (10%)
6 (12%)
23 (9%)

Chemotherapy

53 (18%)
19 (37%)
34 (14%)

Lu-PSMA

28 (10%)
0 (0%)
28 (11%)

ARSI

163 (55%)
26 (50%)
137 (56%)

PARPi +/- ARSI

1 (0.3%)
0 (0%)
1 (0.4%)

Radium

20 (7%)
0 (0%)
20 (8%)

None/Other/NA

2 (1%)
1 (2%)
1 (0.4%)

Treatment 2nd line mCRPC
296

<0.001

Chemotherapy

69 (23%)
27 (52%)
42 (17%)

Lu-PSMA

73 (25%)
0 (0%)
73 (30%)

ARSI

114 (39%)
25 (48%)
89 (36%)

PARPi+/- ARSI

5 (2%)
0 (0%)
5 (2%)

Radium

13 (4%)
0 (0%)
13 (5%)

None/Other/NA

22 (7%)
0 (0%)
22 (9%)

1
Median (IQR); n (%).

2
Wilcoxon rank sum test; Fisher’s exact test; Pearson’s Chi-square test.

PSA: Prostate-specific antigen, ECOG: Eastern Cooperative Oncology group, mHSPC: metastatic hormone-sensitive prostate cancer, ADT: Androgen deprivation therapy, ARSI: Androgen receptor signaling inhibitor, PARPi: poly-(ADP-ribose)-polymerase inhibitors, NA: Unknown.