Lutetium-177 PSMA for the treatment of metastatic castrate resistant prostate cancer: a systematic review

Figures & data

Table 1. Radionuclide properties considered for use in targeted therapy. (E_max: Maximum emitted energy, mm: millimeter, MeV: million electron volts).

Radionuclide	Decay type	Half-life (t1/2)	Emission range (mm) in tissue	Emax (MeV)
Yttrium-90 (^90Y) [19]	β^−	64.10 hours	5.30	2.3
Iodine-131 (^131I) [19]	β^−	8.0 days	0.8	0.6
Samarium-153 (^153Sm) [19]	β^−	46.5 hours	0.4	0.8
Lutetium-177 (^177Lu) [19]	β^−	6.6 days	0.62	0.5
Rhenium-186 (^186Re) [19]	β^−	3.72 days	5	1.1
Actinium-225 (^225Ac) [19]	α	10 days	-	5.8

Figure 1. Inclusion and exclusion criteria for systematic review for treatment of metastatic castrate resistant prostate cancer using Lutetium-177 PSMA.

Table 2. Summary of retrospective studies using ¹⁷⁷Lu-PSMA therapy in mCRPC.

Study	Imaging-based PFS (median)	Overall survival (median)	RECIST	PERCIST criteria- SUVmax OR PSMA PET/CT	ECOG performance status improvement	PSA decline >50% (% patients)
Rahbar et al [47]	-	29.4 weeks	-	-	-	32–50% PD: 20%
Kratochwil et al [48]	-	-	-	SUVmax decreased ≥50% in 20% subjects	-	43.3% PD: 27%
Ahmadzadehfar et al [49]	-	-	-	-	-	50% PD: 30%
Rahbar et al [50]	-	-	-	-	No change	31% PD: 23%
Brauer et al [51]	18 weeks	32 weeks	-	-	-	53%
Rahbar et al [52]	-	-	PR: 45% SD: 28%	-	-	45%
Moghadam et al [53]	20 weeks	52 weeks	-	-	-	39.5%
Kemppainen et al [54]	4.9 months	17.2 months	-	-	-	58.7%
Rahbar et al [55]	-	56 weeks	-	-	-	33%
Mirshahvalad et al [56]	-	-	PD: 13% SD: 39.1%	-	-	-
Schneider et al [57]	-	16 months	-	-	-	54%
Soydal et al [58]	-	21 months	-	-	-	33%
Leibowitz et al [59]	-	4.7 months	-	-	-	48%
Tatkovic et al [60]	-	18-month OS: 63.8%	-	18-month OS: SUVmax >15–56.0% SUVmax <15–38%	-	20%
Ahmadzadehfar et al [61]	-	60 weeks	-	-	-	44.2%
Mader et al [62]	3.8 months	8.5 months	-	-	47%	36%

(OS: Overall survival, PD: Progression of disease, SD: Stable disease, PR: Partial response).

Table 3. Summary of real-world analysis of ¹⁷⁷Lu-PSMA therapy in mCRPC.

Study	Imaging-based PFS	Overall survival	RECIST	PERCIST criteria- SUVmax OR PSMA PET/CT	ECOG performance status improvement	PSA decline >50% (% patients)
Khreish et al [63]	5.5 months	14.5 months	-	-	-	52.0% PD: 32.7%
Meyrick et al [64]	4 months	12 months	-	PFS: 6 months	-	56%
Assadi et al [65]	-	62.7 weeks	-	PD: 19% SD: 19%	-	62%

Note: (PFS: Progression-free survival, PD: Progression of disease, SD: Stable disease).

Table 4. Summary of published clinical trials studying¹⁷⁷Lu-PSMA therapy in mCRPC.

Study	Imaging-based PFS	Overall survival	RECIST	PERCIST criteria- SUVmax OR PSMA PET/CT	ECOG performance status improvement	PSA decline >50% (% patients)
Sartor et al [17]	8.7 months	15.3 months	CR: 9.2% PR: 41.8%	-	52.7% showed improvement	46%
Yadav et al [66]	-	16 months	-	Prior therapy SUVmax: 56.7 Post therapy SUVmax: 18.2	Pre therapy: 2.54 ± 0.85 Post therapy: 1.78 ± 0.92 (p = 0.001)	Prior therapy: 275 ng/mL Post therapy: 141.75 ng/mL PD: 20%
Emmett et al [67]	-	50 weeks (median not reached)	PR: 29% SD: 14% PD: 29%	-	-	None
Satapathy et al [68]	4 months	-	OR: 39%	-	-	50%
Hofman et al [69]	8.7 months	15.3 months	OR: 46%	-	-	64%
McBean et al [70]	-	-	-	PR: 35.7% SD: 7.1% PD: 57.1%	-	44.9%
Hofman et al [42]	-	13.5 months (median)	CR: 29% PR: 53%	CR: 10% PR: 30 PD: 27%	-	57%
De Giorgi et al [71]	7.5 months	12.4 months	-	-	-	37.5%
Baum et al [72]	13.7 months	Not reached	PR: 20% SD: 52% PD: 28%	Prior therapy SUVmax: 37.5 Post therapy SUVmax: 15.7 PR: 56% SD: 8% PD: 36%	-	58.9% PD: 11%
Aghdam et al [73]	-	-	-	-	35.7% showed improvement	45.4% PD: 21.4%

Note: (PD: Progressive disease; SD: Stable disease; PR: Partial response; CR: Complete response; OR: Objective response; SUVmax: Maximum standardized uptake value; ng/ml: Nanograms per milliliter; PFS: Progression-free survival; RECIST: Response Evaluation Criteria in Solid Tumors; PSMA PET/CT: Prostate-Specific Membrane Antigen Positron Emission Tomography/Computerized Tomography; PERCIST: Positron Emission Tomography (PET) Response Criteria in Solid Tumors; ECOG: Eastern Cooperative Oncology Group).

Table 5. Ongoing prospective trials of Lu-PSMA in prostate cancer [87].

NCT#	PHASE	INTERVENTION	PRIMARY END POINT
NCT05204927 [76]	III	Two arm in 2:1 ratio Arm 1: Lu-177-PSMA-I&T Arm 2: Abiraterone with prednisone or enzalutamide	Radiographic Progression-Free Survival (rPFS)
NCT04689828 [77] (PSMAfore)	III	Two arm in 1:1 ratio Arm 1: ^177Lu-PSMA-617 Arm 2: Androgen receptor directed therapy (ARDT)	Radiographic Progression-Free Survival (rPFS)
NCT04419402 [78] (ENZA-p)	II	Two arm: Enzalutamide or Enzalutamide with ^177Lu-PSMA-617	Prostate Specific Antigen (PSA), progression-Free Survival
NCT05340374 [79] (LuCAB)	Phase I/II	Single arm: Cabazitaxel + Lu-PSMA over 18 months	Dose limiting toxicity, Maximum tolerated dose (MTD), recommended phase 2 dose
NCT03874884 [80] (LuPARP)	Phase I	Single arm: Olaparib + Lu-PSMA for upt o 4 cycles	Dose limiting toxicity, maximum tolerated dose (MTD), recommended phase 2 dose
NCT05383079 [81] (AlphaBet)	I/II	Single arm: Lu-177 in combination with Radium 223	Dose limiting toxicities, maximum tolerated dose (MTD), Prostate-specific antigen response rate (PSA-RR)
NCT05113537 [82] (UPLIFT)	I/II	Single arm Experimental: Part A: Abemaciclib, ^177Lu-PSMA-617 Part B: recommended dose of abemaciclib followed by Lu-177	Recommended phase 2 dose, dose limiting toxicities
NCT05613894 [83] (CaboLu)	IB	Single arm: Cabozantinib and Lu-177	Dose-limiting toxicities (DLTs)
NCT03805594 [84]	I	Single arm: Lu-177 PSMA-617 and Pembrolizumab	Objective response rate by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
NCT03658447 [85] (PRINCE)	I/II	Single arm: Pembrolizumab up to 35 cycles and Lu-177 up to 6 cycles	Prostate Specific Antigen (PSA) response, treatment-emergent adverse events, tolerability
NCT05150236 [86] (EVOLUTION)	Phase II	Two arm: Ipi/Nivo + Lu-PSMA vs Lu-PSMA alone in 2:1 ratio stratified by prior docetaxel exposure	PSA progression-free survival (PSA-PFS) at 1 year

Note: (PSA: Prostate-specific antigen, PSA-PFS: Prostate-specific antigen-based progression-free survival, OS: Overall survival).

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