Abstract 601P
Background
Baseline plasma AR CN is a promising biomarker for mCRPC outcome and treatment response; however, the role of its longitudinal testing is unproven. We aimed to evaluate the prognostic role of AR CN assessed prior to each treatment line in mCRPC patients (pts).
Methods
A subgroup analysis of a prospective biomarker trial was performed retrieving mCRPC pts who received docetaxel, cabazitaxel and an AR signaling inhibitor (ARSI: abiraterone or enzalutamide). Treatment sequence was chosen according to clinical practice. Plasma AR CN status (classified as normal or gain, cut off value=2) was assessed with digital PCR prior to each treatment line and correlated with clinical outcomes. Data are expressed as median, hazard ratio (HR) and [95% CI].
Results
Forty pts were enrolled from 2015 to 2018; median follow up was 89 months (range: 11-111). As first-line, 23 pts received docetaxel and 17 ARSI; overall median PFS was 6.8 and OS 50.8 months. As second-line, 17 received docetaxel, 12 cabazitaxel and 11 ARSI; overall median PFS was 6.6 and OS 28.4 months. As third line, 28 received cabazitaxel and 12 ARSI; overall median PFS was 5.2 and OS 16.6 months. In the 3 subsequent assessments, AR CN status was normal in all samples in 15 (38%) pts, changed from normal to gain in 15 (38%),was gain in all samples in 10 (24%). According to these groups, median OS was 69 (reference), 47 (HR 2.4 [1.0-5.8]), and 37 months (HR 4.9 [1.8-12.9]) (p=0.01), respectively. At multivariate analysis, at each assessment OS was independently correlated with AR CN status (first-line: HR 4.1 [1.6-10.5]; second-line: HR 2.4 [1.1-5.3]; third line: HR 2.1 [1.0-4.3]) and median PSA (first-line: HR 4.4 [1.8-10.9]; second-line: HR 3.4 [1.6-7.2]; third line: HR 2.5 [1.2-5.6]).
Conclusions
Plasma AR CN correlates with OS not only at baseline (prior to first-line), but also in the assessments prior to the following lines. Interestingly, AR CN status may change from normal to gain across subsequent treatments in a significant amount of cases, identifying a group of pts with intermediate outcomes. Longitudinal assessment of AR CN status could represent a promising method to capture mCRPC intrinsic heterogeneity.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
N. Brighi: Other, Institutional, Other, travel support/speaker honoraria: Pfizer; Other, Institutional, Other, travel support/speaker honoraria: Novartis; Other, Institutional, Other, travel support/speaker honoraria: Ipsen. V. Conteduca: Other, Institutional, Advisory Board: Janssen; Other, Institutional, Advisory Board: Astellas; Other, Institutional, Advisory Board: Merck; Other, Institutional, Advisory Board: AstraZeneca; Other, Institutional, Advisory Board: Bayer; Other, Institutional, Other, speaker honoraria/travel support: Astellas; Other, Institutional, Other, speaker honoraria/travel support: Janssen; Other, Institutional, Other, speaker honoraria/travel support: Ipsen; Other, Institutional, Other, speaker honoraria/travel support: Bayer; Other, Institutional, Other, speaker honoraria/travel support: Sanofi. G. Gurioli: Other, Institutional, Other, travel support: Sanofi Genzyme. C. Lolli: Other, Institutional, Advisory Board: Bristol-Myers Squibb; Other, Institutional, Advisory Board: Janssen-Cilag. U. De Giorgi: Other, Institutional, Advisory Board: Bristol-Myers Squibb; Other, Institutional, Advisory Board: Astellas; Other, Institutional, Advisory Board: Bayer; Other, Institutional, Advisory Board: Janssen; Other, Institutional, Advisory Board: Ipsen; Other, Institutional, Advisory Board: Merck; Other, Institutional, Advisory Board: Pfizer; Other, Institutional, Advisory Board: Sanofi; Other, Institutional, Other, travel support: Bristol-Myers Squibb; Other, Institutional, Other, travel support: Ipsen; Other, Institutional, Other, travel support: Bayer; Other, Institutional, Other, travel support: Pfizer; Other, Institutional, Funding: AstraZeneca; Other, Institutional, Funding: Roche; Other, Institutional, Funding: Sanofi. All other authors have declared no conflicts of interest.