Efficacy and side effects of lutetium-¹⁷⁷PSMA-617 in patients with castration resistant metastatic prostate cancer: a systematic review and meta-analysis

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Resumo

Introduction. Progression of metastatic prostate cancer after castration resistance is one of the main challenges in prostate cancer therapy. ¹⁷⁷Lu-PSMA-617 has been recently investigated in castration resistant metastatic prostate cancer.

Objectives. To systematically evaluate the efficacy and safety profile of ¹⁷⁷Lu-PSMA- 617.

Patients and methods. A systematic review and meta-analysis was conducted according PRISMA principles. From initial 261 results, 3 randomized controlled trials met our inclusion criteria. The primary outcome of this study was oncological response and side effects. RevMan 5,4 software was applied in this systematic review and meta- analysis.

Results. A total of 1071 patients were included in the pooled analysis. 670 (62,6%) patients received ¹⁷⁷Lu-PSMA-617. Progression-free survival was significantly better with a hazard ratio of 0,72 (p= 0,00001). 50%>PSA reduction reported in 75 (63%) vs. 45/121 patients (37,2%) (p=0,0001). Total adverse events recorded in 572 / 627 (91,2%) developed AEs, vs. 204 / 290 (70,3%) (p = 0,00001). Fatigue was reported in 306/647 (47,3%) patients vs 88/310 (28,4%) (p=0,00001). And constipation in 110/549 (20%) vs 24/225 (10,7%) (p=0,003). Both thrombocytopenia and leucopoenia were marginally significantly higher in 114 / 647 (17,6%) vs 19 / 310 (6,1%) (p=0,08) and 81 / 647 (12,5%) vs 13 / 310 (4,2%) (p=0,10), respectively.

Conclusion. ¹⁷⁷Lu-PSMA-617 results in significant reduction in PSA and improves the progression-free survival. It can cause tolerable side effects, mainly fatigue, constipation, thrombocytopenia and leucopoenia.

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Sobre autores

Omar Fahmy

Department of Urology, Faculty of Medicine and Science Health Universiti Putra; Department of Urology, Hospital Sultan Abdul Aziz Shah Universiti Putra

Autor responsável pela correspondência
Email: omarfahmy.ahmed@upm.edu.my
ORCID ID: 0000-0002-1631-2733

MBBS, MRCS (England), Masters Urology (Zagazig), FRCS Urology (Glasgow), Associate Professor and Consultant Urologist of Department of Urology, Faculty of Medical Science and Health

 

Malásia, Malaysia; Persiaran Mardi-UPM, 43400 Serdang, Malaysia

Razaleigh Mohd

Department of Urology, Hospital Sultan Abdul Aziz Shah Universiti Putra

Email: razaleighyusof@yahoo.com
ORCID ID: 0000-0003-1596-9415

M.D., MMed Surgery, FRCS Urology, Consultant Urologist Department of Urology, Hospital Sultan Abdul Aziz Shah

Malásia, Persiaran Mardi-UPM, 43400 Serdang, Malaysia

Mohd Khairul Asri

Department of Urology, Faculty of Medicine and Science Health Universiti Putra; Department of Urology, Hospital Sultan Abdul Aziz Shah Universiti Putra

Email: drkhairulasri@gmail.com
ORCID ID: 0000-0002-5026-5432

M.D., Masters Surgery, FRCS Urology, Professor and Consultant Urologist Department of Urology, Faculty Medicine and Science Health

Malásia, Malaysia; Persiaran Mardi-UPM, 43400 Serdang, Malaysia

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2. Figure 1. CONSORT diagram for the screening and selection processes of the included studies

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3. Figure 2. Total percentage risk of bias for all the randomized trials: green, low risk; yellow, unclear; red, high risk

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4. Figure 3. Risk of bias in the randomized trials: green, low risk; yellow, unclear; red, high risk

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5. Figure 4. Forest plot for the effect of ¹⁷⁷Lu-PSMA-617 on PSA response (a) and progression-free survival (b)

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6. Figure 5. Forest plot for the comparison between ¹⁷⁷Lu-PSMA-617 patients and controls in a) adverse events, b) fatigue, c) pain, d) nausea e) vomiting

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7. Figure 6. Forest plot for the comparison between ¹⁷⁷Lu-PSMA-617 patients and controls in a) diarrhoea, b) constipation, c) anaemia, d) thrombocytopenia e) leucopoenia

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8. Figure 7. Forest plot for the comparison between ¹⁷⁷Lu-PSMA-617 patients and controls in a) dose reduction, b) discontinuation, c) mortality

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