Potential biomarkers of overall survival outcomes have been identified in an exploratory post-hoc analysis of the phase 3 TITAN trial.
In patients with metastatic castration-sensitive prostate cancer (mCSPC) treated with apalutamide (Erleada) plus androgen-deprivation therapy (ADT), potential biomarkers of overall survival (OS) outcomes have been identified in an exploratory post-hoc analysis of the phase 3 TITAN trial.
Specifically, “Detection of circulating tumor (ct)DNA or select androgen receptor (AR) and non-AR biomarkers at baseline or end of study treatment (EOST) may be associated with worse survival [with apalutamide/ADT] among patients with mCSPC,” lead study author Neeraj Agarwal, MD, Huntsman Cancer institute, and coauthors wrote in a poster they shared at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting.
Overall, the TITAN trial (NCT02489318) randomized 1052 patients with mCSPC 1:1 to receive apalutamide plus ADT or placebo plus ADT. Results of the primary and final analyses of the trial showed that adding apalutamide to ADT led to a significant benefit in OS and radiographic progression-free survival versus ADT alone.
For the biomarker analysis, Agarwal et al used next-generation sequencing to analyze ctDNA and genomic aberrations in 17 prostate cancer–related genes at baseline and at EOST. Baseline data were available for 114 patients and EOST data were available for 129 patients. Using statistical modeling, the investigators evaluated associations of ctDNA/aberrations detected at baseline and EOST with OS, as well as associations of ctDNA/aberrations detected at EOST with OS on subsequent therapies.
The investigators reported that the following aberrations occurred in ≥15% of the baseline population across both treatment arms: any genomic AR aberration, AR amplification, TP53,
HRR pathway (BRCA1, BRCA2, FANCA, BRIP1, HDAC2, CDK12, ATM, PALB2, and CHEK2), RB1, PTEN, and PIK3CA.
At baseline, 36% (41/114) of patients had detectable ctDNA, of which 27% (11/41) had any genomic AR aberration and 24% (10/41) had AR gene amplification. In this period from baseline to EOST, there was a significant increase in the presence of these biomarkers. At EOST, 75% (97/129) of patients had detectable ctDNA, of which 67% (65/97) had any genomic AR aberration and 63% (61/97) had AR gene amplification. All of these increases were statistically significant (P <.001 for EOST vs BL for all 3).
There was also an increase in the most prevalent non-AR aberrations at BL, however none of these increases was statistically significant:
The investigators also reported that multivariate analyses from both treatment groups showed that the baseline biomarkers of ctDNA (HR, 1.92; 95% CI, 1.11-3.31; P = .0190) and any AR genomic aberrations (HR, 6.68; 95% CI, 1.68-26.49; P = .0069) were significantly associated with poor OS.
Similarly, multivariate analyses from both treatment groups also showed that the EOST biomarkers of any AR genomic aberration (HR, 1.65; 95% CI, 1.02-2.69; P = .0431) and PI3K pathway aberrations (HR, 2.23; 95% CI, 1.39-3.59; P = .0009) were associated with poor OS.
The researchers also conducted univariate analyses of the population of patients who were treated with subsequent therapy, comprised of 106 patients who received chemotherapy and 161 patients who received hormonal therapy. The only notable findings with this assessment was that, among patients receiving chemotherapy, OS was worse among patients with PIK3CA activation (HR, 3.7; P < .05), PI3K pathway activation (HR, 2.4; P <.05), or TP53 inactivation (HR, 3.0; P <.01) at EOST.
In their poster summary, Agarwal et al noted, “The predictive value of these biomarkers for survival in mCSPC needs further confirmation.”
Reference
Agarwal N, Lucas J, Aguilar-Bonavides C, et al. Genomic aberrations associated with overall survival (OS) in metastatic castration-sensitive prostate cancer (mCSPC) treated with apalutamide (APA) or placebo (PBO) plus androgen deprivation therapy (ADT) in TITAN. J Clin Oncol 40, 2022 (suppl 16; abstr 5066). doi: 10.1200/JCO.2022.40.16_suppl.5066
Lenalidomide Break Possible? Study Shows Hope for MRD-Negative Myeloma
October 7th 2024A new study suggests that patients with multiple myeloma who achieve sustained MRD-negativity for at least three years may be able to discontinue maintenance therapy without compromising their long-term outcomes.
Read More