Safety Analyses of the Phase 3 VISION Trial of [ 177 Lu]Lu-PSMA-617 in Patients with Metastatic Castration-resistant Prostate Cancer

被引：12

作者：

Chi, Kim N. ^{[1
,21
]}

Armstrong, Andrew J. ^{[2
]}

Krause, Bernd J. ^{[3
]}

Herrmann, Ken ^{[4
,5
]}

Rahbar, Kambiz ^{[6
]}

de Bono, Johann S. ^{[7
,8
]}

Adra, Nabil ^{[9
]}

Garje, Rohan ^{[10
]}

Michalski, Jeff M. ^{[11
]}

Kempel, Mette M. ^{[12
,13
]}

Fizazi, Karim ^{[14
]}

Morris, Michael J. ^{[15
]}

Sartor, Oliver ^{[16
]}

Brackman, Marcia ^{[17
]}

Desilvio, Michelle ^{[18
]}

Wilke, Celine ^{[19
]}

Holder, Geoffrey ^{[19
]}

Tagawa, Scott T. ^{[20
]}

机构：

[1] Vancouver Prostate Ctr, British Columbia Canc, Vancouver, BC, Canada

[2] Duke Univ, Duke Canc Inst Ctr Prostate & Urol Canc, Durham, NC USA

[3] Rostock Univ Med Ctr, Dept Nucl Med, Rostock, Germany

[4] Univ Duisburg Essen, Dept Nucl Med, Essen, Germany

[5] Univ Hosp Essen, German Canc Consortium DKTK, Essen, Germany

[6] Univ Hosp Munster, Dept Nucl Med, Munster, Germany

[7] Inst Canc Res, Div Clin Studies, London SW3 6JJ, England

[8] Royal Marsden Hosp, London, England

[9] Indiana Univ Melvin & Bren Simon Comprehens Canc C, Indianapolis, IN USA

[10] Miami Canc Inst, Baptist Hlth South Florida, Miami, FL USA

[11] Washington Univ, Dept Radiat Oncol, St Louis, MO USA

[12] Aalborg Univ Hosp, Dept Oncol, Aalborg, Denmark

[13] Aalborg Univ Hosp, Clin Canc Res Ctr, Aalborg, Denmark

[14] Univ Paris Saclay, Inst Gustave Roussy, Dept Canc Med, Villejuif, France

[15] Mem Sloan Kettering Canc Ctr, Genitourinary Oncol Serv, New York, NY USA

[16] Tulane Univ Sch Med, Tulane Canc Ctr, New Orleans, LA USA

[17] Novartis Pharmaceut, Indianapolis, IN USA

[18] Novartis Pharmaceut, Biostat, E Hanover, NJ USA

[19] Novartis Pharm AG, Basel, Switzerland

[20] Hematol & Med Oncol Dept, Weill Cornell Med, New York, NY USA

[21] British Columbia Canc, 686 West Broadway, Vancouver, BC V5Z1G1, Canada

来源：

EUROPEAN UROLOGY | 2024年 / 85卷 / 04期

关键词：

Metastatic castration-resistant; prostate cancer; Radioligand therapy; Lu-177-PSMA-617; Treatment-emergent adverse; events; Treatment exposure; RADIOLIGAND THERAPY; OPEN-LABEL; MULTICENTER; EFFICACY;

D O I：

10.1016/j.eururo.2023.12.004

中图分类号：

R5 [内科学]; R69 [泌尿科学（泌尿生殖系疾病）];

学科分类号：

1002 ; 100201 ;

摘要：

Background and objective: [Lu-177]Lu-PSMA-617 (Lu-177-PSMA-617) plus the standard of care (SoC) significantly improved overall survival and radiographic progression-free survival versus SoC alone in patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer in the VISION trial. We evaluated the safety of additional cycles of Lu-177-PSMA-617 and the impact of longer observation time for patients receiving Lu-177-PSMA-617 plus SoC. Methods: VISION was an international, open-label study. Patients were randomised 2:1 to receive Lu-177-PSMA-617 plus SoC or SoC alone. The incidence of treatment-emergent adverse events (TEAEs) was assessed in prespecified subgroups of patients who received <= 4 cycles versus 5-6 cycles of treatment and during each cycle of treatment. The TEAE incidence was also adjusted for treatment exposure to calculate the incidence per 100 patient-treatment years of observation. This analysis was performed for the first occurrence of TEAEs. Key findings and limitations: The any-grade TEAE incidence was similar in cycles 1-4 and cycles 5-6. TEAE frequency was similar across all cycles of Lu-177-PSMA-617 treatment. No additional safety concerns were reported for patients who received >4 cycles. The exposure-adjusted safety analysis revealed that the overall TEAE incidence was similar between arms, but distinct trends for different TEAE types were noted and the incidence of events associated with Lu-177-PSMA-617 remained higher in the Lu-177-PSMA-617 arm. Conclusions and clinical implications: Longer exposure to Lu-177-PSMA-617 plus SoC was not associated with a higher toxicity risk, and the extended time for safety observation could account for the higher TEAE incidence in comparison to SoC alone. The findings support a favourable benefit-risk profile for 6 cycles of Lu-177-PSMA-617 in this setting and the use of up to 6 cycles of Lu-177-PSMA-617 in patients who are clinically benefiting from and tolerating this therapy. Patient summary: For patients with metastatic prostate cancer no longer responding to hormone therapy, an increase in the number of cycles of treatment with a radioactive compound called Lu-177-PSMA-617 from four to six had no additional adverse side effects.

引用

页码：382 / 391

页数：10

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