Prospective phase 2 trial of PSMA-targeted molecular RadiothErapy with 177Lu-PSMA-617 for metastatic castration-reSISTant Prostate Cancer (RESIST-PC): efficacy results of the UCLA cohort

Jeremie Calais; Andrei Gafita; Matthias Eiber; Wesley R. Armstrong; Jeannine Gartmann; Pan Thin; Kathleen Nguyen; Vincent Lok; Laura Gosa; Tristan Grogan; Rouzbeh Esfandiari; Martin Allen-Auerbach; Andrew Quon; Shadfar Bahri; Pawan Gupta; Linda Gardner; David Ranganathan; Roger Slavik; Magnus Dahlbom; Ken Herrmann; Ebrahim Delpassand; Wolfgang P. Fendler; Johannes Czernin

doi:10.2967/jnumed.121.261982

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FIGURE 1.
Waterfall plots showing PSA changes relative to baseline after 2 cycles of ¹⁷⁷Lu-PSMA (A) and any time during treatment (B).
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FIGURE 2.
Survival Kaplan–Meier curves. Kaplan–Meier curves for PSA PFS (A) and OS (B) by treatment arm. Tick marks indicate censored data. The log-rank test is given with P < 0.05 considered significant.
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FIGURE 3.
Kaplan–Meier curves for OS by PSA response after 2 cycles (A) and at any time (B). Tick marks indicate censored data. The log-rank test is given with P < 0.05 considered significant.

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TABLE 1

Characteristics of Study Population at Baseline

Characteristic	Overall (n = 43)	6.0 GBq (n = 14)	7.4 GBq (n = 29)
Age (y)	74 (68–78)	76 (70–79)	72 (65–78)
Time since diagnosis of PCa (y)	7 (4–17)	8 (5–17)	7 (4–15)
Gleason grade group at diagnosis^*
≥4	25 (64%)	9 (69%)	16 (62%)
PSA (ng/mL)	27.4 (9.5–115.6)	31.3 (12.6–160.2)	26.1 (9.5–124.4)
PSA doubling time (mo)	1.5 (1.0–2.3)	1.3 (1.0–1.7)	1.8 (1.0–3.2)
Total alkaline phosphatase (U/I)	87 (67–125)	82 (60–175)	94 (69–117)
Hemoglobin (g/dL)	12.0 (10.9–13.2)	12.1 (11.2–12.9)	11.6 (10.8–13.3)
Platelets (10³/mL)	208 (160–245)	207 (163–356)	208 (158–238)
ECOG performance status
0	13 (30%)	8 (57%)	5 (17%)
1	21 (49%)	4 (29%)	17 (59%)
2	9 (21%)	2 (14%)	7 (24%)
Pain at baseline (BPI score)
No pain	21 (49%)	4 (28%)	17 (58%)
Mild (1–4)	11 (26%)	5 (36%)	6 (21%)
Moderate to severe (5–10)	11 (26%)	5 (36%)	6 (21%)
Previous mCRPC systemic treatments
Chemotherapy regimen lines
0	11 (26%)	4 (29%)	7 (24%)
1	10 (23%)	4 (29%)	6 (21%)
2	12 (28%)	3 (21%)	9 (31%)
≥3	10 (23%)	3 (7%)	7 (24%)
Abiraterone	41 (95%)	13 (93%)	28 (97%)
Enzalutamide	37 (86%)	13 (93%)	24 (83%)
Abiraterone + enzalutamide	35 (82%)	12 (86%)	23 79%)
²²³Ra	14 (33%)	4 (29%)	10 (35%)
Prior lines of mCRPC systemic treatment
1	4 (9%)	1 (7%)	3 (10%)
≥2	39 (91%)	13 (93%)	26 (90%)
≥3	31 (72%)	10 (71%)	21 (72%)
≥4	25 (58%)	8 (57%)	17 (59%)
Extent of disease on PSMA-PET
≤20 metastases	14 (33%)	4 (29%)	10 (34%)
2 metastases	29 (67%)	10 (71%)	19 (66%)
Sites of disease on PSMA PET
Node only (N1 or M1a)	3 (7%)	1 (7%)	2 (7%)
Bone only (M1b)	9 (21%)	3 (21%)	6 (21%)
Node + bone (M1b and [N1 or M1a])	15 (35%)	7 (50%)	8 (28%)
Visceral (M1c with/without any other site)^†	15 (35%)	3 (21%)	12 (41%)

↵* Data missing for 4 patients.
↵† Visceral includes lung, liver, rectum, pancreas, peritoneal, brain, and adrenal.
BPI = bone pain index.
Data are median, with IQR in parentheses, or n (%).

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TABLE 2

Primary and Secondary Endpoints Results

Outcome measure	Overall (n = 43)	6.0 GBq (n = 14)	7.4 GBq (n = 29)	Hazard ratio (95% CI)	P
Primary endpoint
PSA response after 2 cycles
No. of evaluable patients	40	13	27
PSA decline ≥ 50% after 2 cycles	11 (28%, 95% CI 15–44)	6 (46%, 95% CI 19–75)	5 (19%, 95% CI 6–38)	—	0.12^*
Secondary endpoint
Best PSA response
No. of evaluable patients	43	14	29
Best PSA response ≥ 50%	16 (37%, 95% CI 23–53)	7 (50%, 95% CI 23–77)	9 (31%, 95% CI 15–51)	—	0.31^*
Pain response
No. of evaluable patients	18	7	11
Patients with pain improvement (n)	12 (67%)	6 (86%)	6 (55%)	—	0.31^*
Pain PFS
Median (mo)	8.2 (95% CI 3.9–12.5)	5.4 (not reached)	8.2 (95% CI 2.3–14.1)	0.96 (0.35–2.66)	0.94
Post hoc analysis
OS
Median (mo)	14.0 (95% CI 10.1–17.9)	15.8 (95% CI 11.8–19.4)	13.5 (95% CI 10.0–17.0)	0.94 (0.46–1.92)	0.87