Circulating tumor DNA monitoring in ovarian cancer patients receiving PARPi maintenance therapy: Can we further personalize treatment?
Recommendations for the length of maintenance therapy with poly (ADP-ribose) polymerase inhibitors (PARPi) in patients with ovarian cancer (OC) are derived from clinical trials with various durations of therapy. Here, we evaluated whether circulating tumor DNA (ctDNA) predicted recurrence/progression in OC patients receiving PARPi maintenance. This was a multi-center retrospective cohort study of real-world data from commercial ctDNA testing (Signatera™, Natera, Inc.) in patients with OC on PARPi maintenance following response to penultimate platinum-based therapy. Clinical data were collected on stage, setting, pathologic subtype, and biomarker status. Fifty-three patients with OC were analyzed, with samples collected: i) prior to starting PARPi (pre-PARPi; N = 12), ii) during the first 12 months on PARPi (early; N = 34), and iii) beyond 12 months of PARPi therapy (late; N = 26). ctDNA was detected prior to PARPi initiation in 58 % (7/12) of patients, and none experienced sustained ctDNA clearance on PARPi therapy. Notably, none of the ctDNA-negative patients recurred at the last known clinical follow-up. Persistent/conversion to ctDNA positivity within the first 3 months of therapy was associated with significantly shorter progression-free survival (PFS) (p = 0.01). Patients who were serially ctDNA-negative/cleared ctDNA within 6 months on therapy had significantly improved PFS compared to those who were persistently positive/converted to positive (p = 0.003). Correlation with CA-125 and BRCA/HR status was not significant. ctDNA status on-PARPi was a stronger predictor of disease progression compared to CA-125 or BRCA/HR status. While additional analyses are warranted, our data suggest that ctDNA is a promising biomarker for therapeutic decision-making.