Circulating Tumor DNA Analyses in Metastatic Castration-Resistant Prostate Cancer
Posted: Tuesday, July 21, 2020
For patients with metastatic castration-resistant prostate cancer, circulating tumor DNA may provide valuable information on disease progression and patient prognosis, according to findings presented during the ASCO20 Virtual Scientific Program (Abstract 5508). The phase II A.MARTIN study demonstrated that this strategy may identify patients with a poor prognosis at baseline and may inform treatment response as well as radiologic progression-free survival, according to Johann S. De Bono, PhD, of the Royal Marsden Hospital and the Institute of Cancer Research, London, and colleagues.
“[Circulating tumor DNA] can elucidate emerging resistance mechanisms at disease progression,” the authors observed.
The investigators collected blood samples from 216 patients with metastatic castration-resistant prostate cancer at three points: baseline; cycle 3, day 1; and end of treatment. Cell-free DNA was extracted from plasma using a circulating DNA kit. Patients were treated with or without the AKT inhibitor ipatasertib.
Baseline positivity for circulating tumor DNA correlated positively with radiologic progression-free survival (hazard ratio = 1.8), and this association was preserved in a multivariate Cox model with fewer than five baseline clinical valuables (hazard ratio = 1.6). Patients with a reduction in circulating tumor DNA at cycle 3, day 1 exhibited better radiologic progression-free survival than those with an increase in circulating tumor DNA.
In addition, changes in circulating tumor DNA were associated with the best confirmed overall response. For instance, patients with a complete responsive had the greatest reduction in circulating tumor DNA (a mean of –23.4% ), followed by patients with a partial response (–16.%), stable disease (–4.1%), and progressive disease (–1.3%). Changes in circulating tumor DNA also correlated with solid tumor changes and prostate-specific antigen changes.
Finally, the presenters also explored copy number variations. They found emerging resistance mutations in progressive samples, including alterations in TP53, AR, FOXA, PTEN, and PI3K/AKT pathway genes.
Disclosure: For full discourses of the study authors, visit coi.asco.org.