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1836P Blood based biomarkers identify metastatic castration-resistant prostate cancer (mCRPC) with the greatest benefit from continuing enzalutamide (ENZ) beyond progression in combination with docetaxel (Doc): A pre-specified biomarker study of the phase IIIb PRESIDE trial

2023; Elsevier BV; Volume: 34; Linguagem: Inglês

10.1016/j.annonc.2023.09.2784

1569-8041

M. Ruiz Vico, Daniel Wetterskog, S. Thakali, Francesco Orlando, Anuradha Jayaram, Osvaldas Vainauskas, D.E. Castellano Gauna, Karla Martins, Kenneth K. Iwata, G. Gourgioti, A. Serikoff, Lennart Åström, В. Б. Матвеев, Adil Esen, Susan Feyerabend, Elżbieta Senkus, Sumati Gupta, Axel S. Merseburger, Francesca Demichelis, Gerhardt Attard,

Radiopharmaceutical Chemistry and Applications

PRESIDE (NCT02288247) was a randomised, international trial that met its primary endpoint of prolonged progression-free survival (PFS) with continued ENZ beyond progression in patients (pt) starting Doc. A pre-specified aim of PRESIDE was to test for androgen receptor (AR) blood-based biomarkers to test for differential benefit. Pt who participated in PRESIDE, consented to the biomarker sub-study and donated blood at randomization (Period 2 baseline, P2BL) were included. Blood was also collected on treatment (P2 Week [W] 4 and 13), progression and follow up. Pre-specified primary objectives were to evaluate PFS for 1) ENZ versus (v) Placebo (P) in pt split by +/- plasma AR gain or AR-V7 in circulating tumor cells (CTC) at P2BL and 2) PFS for all pt split by +/- tumor in plasma DNA (ptDNA) at P2W4. Custom targeted next-generation sequencing on plasma DNA was performed using a bespoke panel (PCF SELECT). Identification of CTC +/- AR-V7 in whole blood samples was performed by Epic Sciences (San Diego, California). Of 271 pt randomised to ENZ / P, 157 (57.9%, 79 on ENZ + Doc, 78 on P + Doc) donated blood. 100 (64%) were plasma AR wild type (wt), 56 (36%) had AR gain. 126 (80%) were AR-V7 negative (-), 17 (11%) AR-V7 positive (+). AR status not available for plasma DNA (1 pt) and CTC (14 pt, 9%). Pt who were AR wt and AR-V7- (N=87, 55%) had significantly prolonged PFS from continuing ENZ (11.2 months (m) v 8.7 m P, HR: 0.49; 95% CI: 0.29-0.82, p=0.006), whilst pt with AR gain or AR-V7+ (N=62) did not (6.2 m ENZ v 7.9 m P; HR: 1.29; p=0.44). Restricted mean survival times at 18 m for AR wt and AR-V7- was 11.5 m ENZ v 8.9 m P, p=0.0046, for AR gain or AR-V7 + was 7.9 m ENZ vs 7.1 m P, p=0.5023. Compared with negative ptDNA at P2W4 (99, 74% of 134 pt included), pt with positive ptDNA (35, 26%) had significantly shorter PFS (5.4 m vs 10.8 m, HR: 1.92; 95% CI: 1.14-3.23, p=0.0145). The benefit of continuing ENZ beyond progression with Doc vs Doc alone is greatest in patient with no evidence of plasma AR gain or AR-V7+ CTC. Plasma tumor DNA detection after 3 weeks Doc +/- ENZ identifies patients with shorter PFS.