177Lu-PSMA-617 and Idronoxil in Men with End-Stage Metastatic Castration-Resistant Prostate Cancer (LuPIN): Patient Outcomes and Predictors of Treatment Response in a Phase I/II Trial

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FIGURE 1.
(A–D) Patient who was eligible on the basis of imaging with PSMA-avid disease (A) and no sites of discordant ¹⁸F-FDG (B). Quantitative PSMA tumor volume (C) and ¹⁸F-FDG tumor volume (D) are also shown. (E–H) Patient who was ineligible on the basis of imaging showing 2 sites (arrows) with higher ¹⁸F-FDG avidity (F) than PSMA avidity (E). Quantitative PSMA tumor volume (G) and ¹⁸F-FDG tumor volume (H) are also shown.
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FIGURE 2.
Waterfall plot of best PSA responses as indicated by maximum percentage change from baseline at any time point. NOX = NOX66.
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FIGURE 3.
Kaplan–Meier curves for PSA progression-free survival (A) and OS (B).
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FIGURE 4
Graphical representation of important markers of OS. (Right) Swimmer plot showing individual-patient PFS and OS. (Left) Graph showing corresponding baseline tumor volume for each patient.

TABLE 1

Patient Characteristics (n = 56)

Characteristic	Data
Age (y)	69 (64–74)
Eastern Cooperative Oncology Group status
0 or 1	49 (88)
2	7 (12)
PSA at C1 (μg/L)	115 (46–476)
Hemoglobin (reference range [RR], 130–180 g/L)	122 (110–131)
Alkaline phosphatase (RR, 30–100 U/L)	113 (86–231)
Albumin (RR, 36–52 g/L)	38 (34–41)
De novo metastatic disease	29 (52)
Gleason score
≤7	9 (16)
8–10	35 (63)
Unknown/not available	12 (21)
Prior systemic treatments
Luteinizing hormone–releasing hormone agonist or antagonist	56 (100)
Chemotherapy	56 (100)
Docetaxel	56 (100)
Cabazitaxel	53 (91)
Other chemotherapy	5 (9)
ASI	56 (100)
Enzalutamide only	27 (48)
Abiraterone only	13 (23)
Abiraterone + enzalutamide	16 (29)
Clinical trial medication	4 (7)
PSMA PET
SUV_mean	8 (7–10)
SUV_max	39 (29–61)
Volume (L)	0.64 (0.19–1.21)
¹⁸F-FDG PET
SUV_mean	4 (3–5)
SUV_max	8 (5–10)
Volume (L)	0.07 (0.02–0.31)
Disease volume
<20 metastases	19 (33)
≥ 0 metastases	37 (66)
Sites of disease on PSMA PET
Bone	49 (88)
Lymph node	31 (55)
Viscera	12 (21)

Qualitative data are absolute counts and percentage; continuous data are median and interquartile range.

TABLE 2

Summary of Common and Therapeutically Relevant Adverse Events (n = 56)

Adverse event	Grade 1	Grade 2	Grade 3	All grades
Anemia	31 (55)	16 (29)	4 (7)	51 (91)
Xerostomia	30 (54)	3 (5)	0 (0)	33 (59)
Fatigue	27 (48)	8 (14)	0 (0)	35 (63)
Anal inflammation	18 (32)	3 (5)	0 (0)	21 (38)
Nausea	15 (27)	0 (0)	0 (0)	15 (27)
Thrombocytopenia	12 (21)	3 (5)	0 (0)	15 (27)
Constipation	11 (20)	1 (2)	0 (0)	12 (21)
Neutropenia	5 (9)	0 (0)	0 (0)	5 (9)
Pneumonitis*	0 (0)	1 (3)	0 (0)	1 (3)

*Attributed to radiation therapy prior to enrollment. Data are number followed by percentage.

TABLE 3

Final Multivariable Model for Association of Baseline Markers with PSA50

	LASSO OR	Multivariable logistic regression			Backward elimination model
Variable	LASSO OR	OR	95% CI	P	OR	95% CI	P
PSMA TV	0.73	0.47	0.20–1.09	0.08	0.42	0.18–0.94	0.04
PSMA SUV_mean	1.20	1.61	1.10–2.34	0.01	1.61	1.12–2.32
Hemoglobin	1.02	1.04	0.99–1.10	0.12	NA	NA	NA

TABLE 4

Final Multivariable Model for Association of Baseline Markers with OS

	LASSO OR	Multivariable Cox regression			Backward elimination model
Variable	LASSO OR	HR	95% CI	P	HR	95% CI	P
PSMA TV	1.67	2.05	1.19–3.53	0.009	2.19	1.381–3.463	0.001
ASI > 12 mo	0.70	0.56	0.24–1.31	0.56	0.42	0.202–0.869	0.02
¹⁸F-FDG tumor volume (L)	NA	0.99	0.25–3.98	0.99	NA	NA	NA
Hemoglobin	0.99	0.98	0.95–1.02	0.30	NA	NA	NA
Presence of visceral disease	1.499	2.01	0.89–4.53	0.09	NA	NA	NA