Prognostic Value of the Circulating Tumor DNA Fraction in Metastatic Castration-resistant Prostate Cancer: Results from the ProBio Platform Trial.
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Crippa Alessio, Laere Bram De, Discacciati Andrea, Larsson Berit, Persson Maria, Johansson Susanne, D'hondt Sanne, Hjälm-Eriksson Marie, Pettersson Linn, Enblad Gunilla, Ullén Anders, Lumen Nicolaas, Karlsson Camilla Thellenberg, Sandzén Johan, Jänes Elin, Ghysel Christophe, Olsson Martha, Sautois Brieuc, Schatteman Peter, Roock Wendy De, Bruwaene Siska Van, Verbiene Ingrida, Darras Jochen, Everaert Els, Maeseneer Daan De, Anden Mats, Strijbos Michiel, Luyten Daisy, Mortezavi Ashkan, Oldenburg Jan, Ost Piet, Lindberg Johan, Grönberg Henrik, Eklund Martin, ProBio Investigators
Аннотация
METHODS: We analyzed data for patients enrolled in the ProBio trial up to November 2022 who received an androgen receptor pathway inhibitor or taxane. We compared survival outcomes between patients with undetectable ctDNA and those with detectable ctDNA randomized to physician's choice or investigational arms. Time to no longer clinically benefiting (NLCB) and overall survival (OS) were assessed using Bayesian survival models, with results reported as survival time ratios (STRs). Dose-response relationships were estimated using spike-at-zero models.
KEY FINDINGS AND LIMITATIONS: A total of 220 patients were included, of whom 139 had detectable ctDNA (56 in the physician's choice arm, 83 in investigational arms) and 81 had undetectable ctDNA. In comparison to the undetectable ctDNA group, the physician's choice arm had 60% shorter time to NLCB (STR 0.40, 90% credible interval [CrI] 0.31-0.51) and 51% shorter OS (STR 0.49, 90% CrI 0.38-0.61). Similar results were observed in comparison to the investigational arms. Dose-response analysis revealed that the undetectable ctDNA group had twofold longer time to NLCB (STR 2.05, 90% CrI 1.66-2.57) and 1.6-fold longer OS (STR 1.63, 90% CrI 1.33-2.05) in comparison to the subgroup with a ctDNA fraction of 2.5%. Every 10-point increment in the ctDNA fraction corresponded to a 10% reduction in NLCB and OS times.
CONCLUSIONS AND CLINICAL IMPLICATIONS: Undetectable ctDNA at baseline predicts superior prognosis in mCRPC, suggesting potential for treatment de-escalation and less intensive monitoring for this subgroup of patients. This trial is registered on ClinicalTrials.gov as NCT03903835.