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

2021; Society of Nuclear Medicine and Molecular Imaging; Volume: 62; Issue: 10 Linguagem: Inglês

10.2967/jnumed.121.261982

1535-5667

Jérémie Calais, Andrei Gafita, Matthias Eiber, Wesley R. Armstrong, J 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 S. Delpassand, Wolfgang P. Fendler, Johannes Czernin,

Prostate Cancer Diagnosis and Treatment

The objective of this study was to determine prospectively the efficacy profile of 2 activity regimens of 177 Lu-PSMA therapy in patients with progressive metastatic castrate-resistant prostate cancer (mCRPC): 6.0 vs. 7.4 GBq. Methods: RESIST-PC (NCT03042312) was a prospective multicenter phase 2 trial. Patients with progressive mCRPC after ≥ 1 novel androgen-axis drug, either chemotherapy naïve or postchemotherapy, with sufficient bone marrow reserve, normal kidney function, and sufficient PSMA expression by PSMA PET were eligible. Patients were randomized (1:1) into 2 activity groups (6.0 or 7.4 GBq) and received up to 4 cycles every 8 wk. The primary endpoint was the efficacy of 177 Lu-PSMA measured by the prostate-specific antigen (PSA) response rate (RR) after 2 cycles (≥50% decline from baseline). Secondary endpoints included the PSA RR (≥50% decline) at any time (best response), and overall survival (OS). Results: The study was closed at enrollment of 71/200 planned patients because of sponsorship transfer. We report here the efficacy of the University of California Los Angeles cohort results only ( n = 43). The PSA RRs after 2 cycles and at any time were 11/40 (28%, 95% CI 15–44), 6/13 (46%, 95% CI 19–75), and 5/27 (19%, 95% CI 6–38), and 16/43 (37%, 95% CI 23–53), 7/14 (50%, 95% CI 23–77), and 9/29 (31%, 95% CI 15–51) in the whole cohort, the 6.0-GBq group, and the 7.4-GBq group, respectively ( P = 0.12 and P = 0.31). The median OS was 14.0 mo (95% CI 10.1–17.9), 15.8 (95% CI 11.8–19.4), and 13.5 (95% CI 10.0–17.0) in the whole cohort, the 6.0-GBq group, and the 7.4 GBq group, respectively ( P = 0.87). OS was longer in patients who experienced a PSA decline ≥ 50% at any time than in those who did not: median, 20.8 versus 10.8 mo ( P = 0.005). Conclusion: In this prospective phase 2 trial of 177 Lu-PSMA for mCRPC, the median OS was 14 mo. Despite the heterogeneous study population and the premature study termination, the efficacy profile of 177 Lu-PSMA appeared to be favorable and comparable with both activity regimens (6.0 vs. 7.4 GBq). Results justify confirmation with real-world data matched-pair analysis and further clinical trials to refine and optimize the 177 Lu-PSMA therapy administration scheme to improve tumor radiation dose delivery and efficacy.