177Lu-Prostate-Specific Membrane Antigen Therapy in Patients with Metastatic Castration-Resistant Prostate Cancer and Prior 223Ra (RALU Study)

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FIGURE 1.
RALU study design. *Data also collected during ¹⁷⁷Lu-PSMA therapy and during follow-up period after last ¹⁷⁷Lu-PSMA dose. ^†Measured from start of ¹⁷⁷Lu-PSMA therapy up to 30 d after last dose. ^‡Measured from start of ¹⁷⁷Lu-PSMA therapy up to 90 d after last dose. ^§Measured from both start of ²²³Ra and start of ¹⁷⁷Lu-PSMA. ^‖Measured from start of ¹⁷⁷Lu-PSMA. ^¶Measured during 60-d baseline period and during follow-up. SAE = serious AE.
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FIGURE 2.
Kaplan–Meier estimates of OS from first dose of ¹⁷⁷Lu-PSMA (A) and first dose of ²²³Ra (B). Descriptive statistics and Kaplan–Meier survival probabilities were generated.
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FIGURE 3.
Kaplan–Meier estimates of OS by time between end of ²²³Ra and start of ¹⁷⁷Lu-PSMA (A) and from first dose of ¹⁷⁷Lu-PSMA by treatment sequence (B). Descriptive statistics and Kaplan–Meier survival probabilities were generated. OS was calculated from first dose of ¹⁷⁷Lu-PSMA. For treatment sequence analysis, 13 patients with multiple taxane-based chemotherapy treatments administered before and after ²²³Ra were included in both groups; patients who did not receive taxane-based chemotherapy (31/133, 23%) were excluded.

TABLE 1.

Baseline Demographics and Clinical Characteristics Before or at Start of ¹⁷⁷Lu-PSMA

Characteristic	Data
Patients	133
Age (y)	73 (49–90)
ECOG PS
1	82 (62)
2	51 (38)
PSA^* (ng/mL) (n = 130)	286 (1–12,229)
ALP^* (U/L) (n = 112)	146 (23–973)
Extent of metastatic disease^†
Bone metastases with lymph node metastases	63 (47)
Bone metastases without lymph node metastases	33 (25)
Visceral metastases	36 (27)
Prior therapies for mCRPC
≥4 life-prolonging therapies^‡	75 (56)
²²³Ra	133 (100)
Injections
1–4	35 (26)
5–6	98 (74)
Abiraterone	95 (71)
Enzalutamide	92 (69)
Abiraterone and enzalutamide	71 (53)
Chemotherapy lines^§
0	31 (23)
1	67 (50)
≥2	35 (26)
Docetaxel	99 (74)
Cycles^‖
1–4	27 (24)
≥5	59 (53)
Missing/unknown	26 (23)
Cabazitaxel	30 (23)
Cycles^¶
1–4	7 (21)
≥5	14 (42)
Missing/unknown	12 (36)

↵* In case of multiple measures, value nearest to ¹⁷⁷Lu-PSMA start was chosen.
↵† Prebaseline period, patient may have multiple metastatic diseases.
↵‡ Docetaxel, cabazitaxel, abiraterone, enzalutamide, ²²³Ra.
↵§ Chemotherapies with same start date ± 15 d were counted as 1 line.
↵‖ n = 112; percentages were based on number of docetaxel therapies (i.e., patients who received 2 lines of docetaxel were counted twice).
↵¶ n = 33; percentages were based on number of cabazitaxel therapies (i.e., patients who received 2 lines of cabazitaxel were counted twice).
ECOG PS = Eastern Cooperative Oncology Group performance status.
Qualitative data are number and percentage; continuous data are median and range.

TABLE 2.

¹⁷⁷Lu-PSMA Therapy

Parameter	Data
Patients	133
Number of ¹⁷⁷Lu-PSMA infusions
1	17 (13)
2	33 (25)
3	16 (12)
4	31 (23)
5	13 (10)
6	14 (11)
>6	9 (7)
Duration of ¹⁷⁷Lu-PSMA therapy (mo)	4.4 (0.0–57.1)
Time from last ²²³Ra injection to first ¹⁷⁷Lu-PSMA dose (mo)^*	12.0 (0.7–74.3)
Time from mCRPC diagnosis to first ¹⁷⁷Lu-PSMA dose (mo)	37.8 (7.4–161.5)
Treatment delay/interruption/cessation^†	51 (38)
Due to disease progression	23 (17)
Due to AE	13 (10)

↵* Last injection from first ²²³Ra treatment cycle in case of multiple cycles.
↵† Patients could have >1 delay and >1 reason for different delays.
Qualitative data are number and percentage; continuous data are median and range. Patients switched to another carrier molecule are reported under first carrier molecule.

TABLE 3.

TEAEs During ¹⁷⁷Lu-PSMA Therapy

		Time between end of ²²³Ra and start of ¹⁷⁷Lu-PSMA^*
Event	All patients (n = 133)	<6 mo (n = 42)	≥6 mo (n = 90)
TEAE
Any grade	105 (79%)	30 (71%)	74 (82%)
Grade 3–4	37 (28%)	15 (36%)	22 (24%)
Serious	40 (30%)	14 (33%)	25 (28%)
TEAEs in ≥10% of patients by PT^†
Dry mouth
Any grade	20 (15%)	3 (7%)	16 (18%)
Grade 3–4	0 (0%)	0 (0%)	0 (0%)
Nausea
Any grade	12 (9%)	5 (12%)	7 (8%)
Grade 3–4	0 (0%)	0 (0%)	0 (0%)
Fatigue
Any grade	11 (8%)	5 (12%)	6 (7%)
Grade 3–4	0 (0%)	0 (0%)	0 (0%)

↵* Time between therapies was unknown in 1 patient and therefore not included in this analysis.
↵† Categories selected by incidence of TEAEs in any group. Excludes laboratory abnormalities.
CTCAE = Common Terminology Criteria for Adverse Events; MedDRA = Medical Dictionary for Regulatory Activities; PT = preferred term.
Data are from start of ¹⁷⁷Lu-PSMA treatment to 30 d after last dose. MedDRA PT is by CTCAE grading.

TABLE 4.

Incidence of Grade 3–4 Laboratory Abnormalities During ¹⁷⁷Lu-PSMA Therapy

Abnormality	All patients	Time between end of ²²³Ra and start of ¹⁷⁷Lu-PSMA^*
Abnormality	All patients	<6 mo	≥6 mo
Anemia	40/133 (30%)	14/42 (33%)	25/90 (28%)
Thrombocytopenia	17/133 (13%)^†	5/42 (12%)	12/90 (13%)
Neutropenia	3/130 (2%)	2/41 (5%)	1/88 (1%)
ASAT elevation	2/131 (2%)	1/42 (2%)	1/88 (1%)

↵* Time between therapies was unknown in 1 patient and therefore not included in this analysis.
↵† Eight of 17 patients had thrombocytopenia at start of ¹⁷⁷Lu-PSMA.
ASAT = aspartate aminotransferase.
Data are from start of ¹⁷⁷Lu-PSMA treatment to 90 d after last dose.