Potential of ctDNA Burden as a Prognostic Biomarker for Efficacy in Patients With mCRPC

The TALAPRO-2 study found that first-line talazoparib and enzalutamide in patients with metastatic castration-resistant prostate cancer (mCRPC) led to increased radiographic progression-free survival (rPFS) when compared with placebo plus enzalutamide.

Research from Arun Azad, MBBS, PhD, and colleagues presented at the 2024 American Society of Clinical Oncology Annual Meeting sought to determine the prognostic value of baseline circulating tumor DNA (ctDNA) burden and evaluated differences in ctDNA burden at week 9 in TALAPRO-2 participants.

Investigators quantified baseline and week 9 serial ctDNA samples through FoundationOneLiquid CDx. ctDNA burden was characterized as high versus low.

Of the patients who received talazoparib plus enzalutamide, 26% were ctDNA-high and 74% were ctDNA-low. Among the placebo plus enzalutamide cohort, 29% were ctDNA-high and 71% were ctDNA low.

Researchers found that in both treatment arms, a high ctDNA burden at baseline was able to predict inferior rPFS. In patients with low ctDNA at baseline and week 9, a relatively positive median rPFS was reported in both the talazoparib plus enzalutamide cohort (n=206) and the placebo plus enzalutamide cohort (n=207). In the talazoparib plus enzalutamide arm, 72 patients were evaluable for ctDNA conversion from high to low at week 9, while in the placebo plus enzalutamide cohort, 77 patients were evaluable.

Dr. Azad and colleagues noted that across therapy groups, conversion from high to low ctDNA was predictive of increased rPFS compared with patients who were ctDNA-high. Those who were ctDNA-low experienced increased rPFS favorability compared with high to low ctDNA.

“High ctDNA burden at [baseline] was negatively prognostic, and ctDNA conversion from high to low at week 9 was prognostic of improved rPFS in TALAPRO-2,” the researchers wrote. “Limitations included not all clinical trial sites were able to perform ctDNA collection and most samples were below the limit of quantification. These results support the broad prognostic utility of ctDNA burden in mCRPC.”